The clinical outcome of abdominoplasty performed under conscious sedation: increased use of fentanyl correlated with longer stay in outpatient unit

The objective of this study was to present data supporting the effectiveness of performing mini and full abdominoplasties under conscious sedation with local anesthesia. The authors performed 20 such operations between 1994 and 1996, using a combination of midazolam (Versed) and fentanyl instead of general anesthesia (without an anesthesiologist or nurse anesthetist present). At 5- to 10-minute intervals, the surgeon would order the injection of 1 cc (1 mg/ml) of midazolam and 1 cc (50 microg/ml) of fentanyl. The amount and the interval varied based on the patient's level of sedation. Blood pressure, oxygen saturation, and the patient's response to verbal and physical stimuli were used to assess the sedation level. Average operating time was 147.5 minutes, and mean length of stay in the outpatient recovery room was 235.5 minutes. The average amounts of midazolam and fentanyl used were 9.4 mg (6 to 12.5 mg) and 532 microg (300 to 800 microg), respectively. The average age of patients in this group was 41.7 years (28 to 63 years). Nineteen patients were discharged the same day. There were no surgical complications and no complication related to the sedation (such as respiratory or cardiac compromise). The average follow-up of these patients was 1.2 years (range, 3 to 21 months). Correlation coefficient rates and regression rates were calculated. The longer the procedure, the more midazolam was used intraoperatively (r = 0.5, p = 0.03). However, there was no correlation between the length of the procedure and the amount of fentanyl used. Rather, there was a positive correlation demonstrating that patients who received more fentanyl stayed longer in the outpatient recovery area after surgery (r = 0.6, p < 0.01). The age of the patients and the amount of midazolam did not correlate with how fast they went home from the outpatient area. In conclusion, full and mini abdominoplasties can be performed safely using conscious sedation without compromising patient care or surgical outcome. Second, the survey revealed that patient satisfaction with these procedures performed under conscious sedation was very high. Third, the increased use of fentanyl, not midazolam, resulted in a longer stay in the outpatient unit after surgery. Nausea is a known side effect of narcotic analgesics, and it correlated with a higher dose of fentanyl administration in the patients. The authors are now routinely administering a dose of either droperidol or odansetron (Zofran) preoperatively (both are antiemetics). Previously, the ratio of midazolam and fentanyl injection was 1:1 every 5 to 10 minutes, but now it is 2: 1 to 4: 1 every 5 to 10 minutes (a smaller dose of fentanyl is administered). The conscious sedation technique should be an option for patients and plastic surgeons in academic and community hospital settings if they desire.     

An outcome study comparing intravenous sedation with midazolam/fentanyl (conscious sedation) versus propofol infusion (deep sedation) for aesthetic surgery

The purpose of this study was to determine the differences in measurable outcomes following aesthetic procedures performed under intravenous sedation with incremental doses of midazolam and fentanyl and those performed under propofol infusion. The authors' hypothesis was that the differences in these outcome parameters are not significant between these intravenous sedation protocols. All intraoperative and perioperative records of 84 consecutive patients having aesthetic surgery under a conscious sedation protocol using incremental doses of intravenous midazolam and fentanyl were retrospectively reviewed and compared with the records of a second group of 85 patients having aesthetic surgery under a deep sedation regimen based primarily on propofol infusion. All procedures were hospital based and performed by two surgeons. Twenty-eight different parameters were examined by chart review. In addition, a patient questionnaire was used to assess patient satisfaction and patient recall of operative and perioperative pain, anxiety, nausea, and vomiting. Multivariate statistical analysis was conducted. The two sedation groups were similar with regard to aesthetic procedures performed and patient demographics. The mean duration of operative time was statistically equivalent (152 minutes and 153 minutes). In both groups, there were minor adverse intraoperative events reported but no significant complications. Transient hypotension was more common in the propofol infusion group (12.9 percent versus 2.4 percent, p = 0.018), but no patient required intervention beyond reducing the sedative agent or increasing intravenous fluids. The amount of supplemental fentanyl given intraoperatively was significantly higher in the group whose primary agent for sedation was propofol infusion than the group who received midazolam/fentanyl (209 mug and 143 mug, respectively). The overall questionnaire response rate was 80 percent for both groups. The midazolam/fentanyl sedation group had more recall of "unpleasant intraoperative events" (17 percent versus 3 percent, p = 0.007). However, both groups had low recall of intraoperative pain, anxiety, and nausea. The propofol infusion group experienced significantly more nausea in the recovery room (p = 0.002), nausea at the time of discharge (p = 0.009), and nausea the evening after the operation (p = 0.013). Greater than 90 percent of the patients in both groups would have the same anesthetic in the future rather than undergo general anesthesia. Patient safety, outcomes, and satisfaction are similar in plastic surgery procedures performed under sedation protocols using either incremental doses of midazolam and fentanyl or propofol infusion. All operative and postoperative outcomes for pain, anxiety, and vomiting were similar in the two groups except for immediate postoperative nausea, which was higher in the propofol infusion group. The overall satisfaction of patients undergoing plastic surgery procedures under these intravenous sedation protocols appears very high.     

Safety and efficacy of office-based surgery with monitored anesthesia care/sedation in 4778 consecutive plastic surgery procedures

Office-based surgery has several potential benefits over hospital-based surgery, including cost containment, ease of scheduling, and convenience to both patients and surgeons. Scrutiny of office-based surgery by regulators and state-licensing agencies has increased and must be addressed by improved documentation of safety and efficacy. To evaluate the safety and efficacy of the authors' office-based plastic surgery, a review was undertaken of 3615 consecutive patients undergoing 4778 outpatient plastic surgery procedures under monitored anesthesia care/sedation in a single office. The charts of 3615 consecutive patients who had undergone office-based surgery with monitored anesthesia care/sedation between May of 1995 and May of 2000 were reviewed. In all cases, the anesthesia protocol used included sedation with midazolam, propofol, and a narcotic administered by a board-certified registered nurse anesthetist with local anesthesia provided by the surgeon. Charts were reviewed for patient profile, types of procedures, multiple procedures, duration of anesthesia, American Society of Anesthesiologists class, and complications related to anesthesia. Outcomes measured included death, airway compromise, dyspnea, hypotension, venous thrombosis, pulmonary emboli, protracted nausea and vomiting lasting more than 24 hours, and unplanned hospital admissions. Statistical analyses were performed using the Microsoft Excel program and the SAS package. Results were as follows: 92.3 percent of the patients were female and 7.7 percent were male, with a mean age of 42.7 years (range, 3 to 83 years). Patients underwent aesthetic (95.6 percent) and reconstructive (4.4 percent) plastic surgery procedures. Same-session multiple procedures occurred in 24.8 percent of patients. The vast majority of patients were healthy: 84.3 percent of patients were American Society of Anesthesiologists class I, 15.6 percent were class II, and 0.1 percent were class III. The operations required a mean of 111 minutes. There were no deaths, ventilator requirements, deep venous thromboses, or pulmonary emboli. Complications were as follows: 0.05 percent (n = 2) of patients had dyspnea that resolved, 0.2 percent (n = 6) of patients had protracted nausea and vomiting, and 0.05 percent (n = 2) of patients had unplanned hospital admissions (<24 hours). One patient had an emergent intubation. No prolonged adverse effects were noted. There was a 30-day follow-up minimum. Outpatient surgery is an important aspect of plastic surgery. It was shown that office-based surgery with intravenous sedation, performed by board-certified plastic surgeons and nurse anesthetists, is safe. Appropriate accreditation, safe anesthesia protocols, and proper patient selection constitute the basis for safe and efficacious office-based outpatient plastic surgery.     

Dissociative anesthesia for safety's sake: ketamine and diazepam--a 35-year personal experience

Recent discussions and proposed rules and regulations regarding outpatient surgery facilities have raised the question of the appropriateness of general anesthesia versus heavy sedation. The controversy is based mostly on anecdotal information and the prejudice of the authors. A recent article that describes the improved platelet function induced by ketamine adds patient safety to the rationale for sedation. Most of us have trained in university settings where an entire department was devoted to general anesthesia and little true outpatient surgery was performed. When ambulatory facilities were available, they were usually staffed by anesthesiologists. Indeed, the first free-standing outpatient surgery center in Phoenix, Arizona, was owned and operated by a local group of anesthesiologists. Properly administered, diazepam and ketamine dissociative sedation is safe and effective for every aesthetic procedure, regardless of size or duration, and it should be available for all aesthetic surgeons. In the author's experience, more than 30,000 procedures have been performed with this method since 1966 without a single case of deep vein thrombosis or pulmonary embolus. In contrast, a former associate, because of his lack of experience, chose to use general anesthesia for a few larger cases in another facility. One of those cases, an abdominoplasty, resulted in a serious case of deep vein thrombosis with subsequent alleged disability and litigation. Therefore, the author is writing to share his extensive experience with his colleagues in hopes that these safe systems will become more widespread and to spare future patients the attendant unnecessary increased morbidity and mortality associated with general anesthesia.     

Factor XI deficiency: implications for management of patients undergoing aesthetic surgery.

We report our experience in patients with an abnormal partial thromboplastin time elevation due to factor XI deficiency (Rosenthal syndrome) who presented for aesthetic surgery consideration. Preoperative evaluation included a thorough history, physical examination, coagulation profile, and hematological consultation. Nine of 10 patients underwent 12 elective aesthetic procedures without undue intraoperative or postoperative bleeding. Based on these findings, we stratified patients as low risk or high risk. Low-risk patients were those with greater than 15 percent factor XI levels, or those with 5 to 14 percent factor XI levels but a history of multiple major surgical procedures without bleeding complications. High-risk patients were those with factor XI levels less than 15 percent, history of bleeding either spontaneously or with surgery, and a family history of bleeding diathesis from factor XI deficiency. Low-risk patients had fresh frozen plasma available for the procedure, whereas high-risk patients received fresh frozen plasma 2 hours before surgery. We conclude that (1) in these patients with abnormally high partial thromboplastin time values and no prior known bleeding disorder, we have identified factor XI deficiency as the prevalent coagulopathy; (2) partial thromboplastin time does not necessarily correlate with factor XI levels; (3) patients can be classified as high or low risk for elective surgery based on factor XI levels and prior surgical or family history; (4) recommendations for perioperative management can be made based on this risk profile; and (5) aesthetic surgery can be performed successfully and safely on patients with factor XI deficiency on a case-by-case basis when appropriate guidelines are enforced.     

Safety and efficacy in an accredited outpatient plastic surgery facility: a review of 5316 consecutive cases

Advances in medicine have improved the delivery of health care, making it more technologically superior than ever and, at the same time, more complex. Nowhere is this more evident than in the surgical arena. Plastic surgeons are able to perform procedures safely in office-based facilities that were once reserved only for hospital operating rooms or ambulatory surgery centers. Performing procedures in the office is a convenience to both the surgeon and the patient. Some groups have challenged that performing plastic surgery procedures in an office-based facility compromises patient safety. Our study was done to determine whether outcomes are adversely affected by performing plastic surgery procedures in an accredited outpatient surgical center. A retrospective review was performed on 5316 consecutive cases completed between 1995 and 2000 at Dallas Day Surgical Center, Dallas, Texas, an outpatient surgical facility. Most cases were cosmetic procedures. All cases were analyzed for any potential morbidity or mortality. Complications requiring a return to the operating room were determined, as were infection rates. Events leading to inpatient hospitalization were also included. During this 6-year period, 35 complications (0.7 percent) and no deaths were reported. Most complications were secondary to hematoma formation (77 percent). The postoperative infection rate for patients requiring a return to the operating room was 0.11 percent. Seven patients required inpatient hospitalization following their procedure secondary to arrhythmias, angina, and pulmonary emboli. Patient safety must take precedence over cost and convenience. Any monetary savings or time gained is quickly lost if safety is compromised and complications are incurred. The safety profile of the outpatient facility must meet and even exceed that of the traditional hospital-based or ambulatory care facility. After reviewing our experience over the last 6 years that indicated few complications and no deaths, we continue to support the judicious use of accredited outpatient surgical facilities by board-certified plastic surgeons in the management of plastic surgery patients.     

Measuring outcomes in aesthetic surgery: a comprehensive review of the literature

Outcomes research examines the end results of medical interventions, taking into account patients' experiences, preferences, and values. The purpose of assessing outcomes is to provide evidence on which to base clinical decisions. The assessment of outcomes in aesthetic surgery is especially pertinent because patient satisfaction is the predominant factor in determining success. In cosmetic surgery, various scales have been used to assess outcomes. Unfortunately, none of these methods has achieved widespread use. The adoption of broadly accepted, relevant scales to measure outcomes would be advantageous, because this would allow the comparison of techniques, quantification of positive effects, and identification of patients unlikely to benefit from surgery. The purpose of this study was to critically review the present literature to identify the appropriate instruments to assess outcomes in aesthetic surgery. After a comprehensive review of aesthetic surgery outcome instruments, the authors identified body-image and quality-of-life measures to be of the greatest value in determining aesthetic surgery outcomes. These conclusions were based on a critical evaluation of the feasibility, validity, reliability, and sensitivity to change of these measures. The Multidimensional Body-States Relations Questionnaire (MBSRQ), a psychological assessment of body image, was selected as a potential candidate for further study. Two additional body-image assessment instruments, the Facial Appearance Sorting Test (FAST) and the Breast Chest Ratings Scale (BCRS), may be useful in the assessment of rhinoplasty and breast surgery, respectively. The Derriford Scale (DAS59), an instrument that assesses appearance-related quality of life, was also selected. In addition, the authors recommend the use of a generic, utility-based quality-of-life instrument, such as the Health Utilities Index (HUI) or the EuroQol (EQ-5D).     

Liposome-encapsulated midazolam for oral administration

The oral administration of midazolam has often been used for sedation in pediatric patients. However, oral administration of an intravenous formulation of midazolam is difficult for younger pediatric patients because of its bitter taste. Liposomes have been developed as vesicles encapsulating various kinds of drugs to serve as a medical drug-delivery system. Thus, the aim of the present study was to produce pH-sensitive liposomes encapsulating midazolam and to evaluate its pharmacokinetics on rabbits. Liposome-encapsulated midazolam was produced from hydrogenated L-α-phosphatidylcholine, cholesterol, dipalmitoylphosphatidic acid, and midazolam. The capacity of liposomes to encapsulate midazolam (encapsulation efficiency), stability of encapsulation, and release efficiency were evaluated in vitro. Further, the produced liposome-encapsulated midazolam solution was orally administered to rabbits in vivo. As a result, midazolam was encapsulated by liposomes with a high encapsulation efficiency and was stably encapsulated in a physiological medium. Further, the produced liposomes rapidly and effectively released midazolam in an acidic medium in vitro. When the liposome-encapsulated midazolam solution was orally administered to rabbits, the time to achieve the maximum plasma concentration of midazolam after administration was slightly longer, but both the maximum plasma concentration and area under the concentration-time curve were higher than those receiving midazolam solution. In conclusion, we produced pH-sensitive liposome-encapsulated midazolam, which remained stable in a physiological medium and showed efficient release in an acidic environment. The results suggest that it is possible to clinically use liposome-encapsulated midazolam for oral administration as a useful drug-delivery vehicle.     

Oral premedication for operations on the face under local anesthesia: a placebo-controlled double-blind trial.

Modern strategies for preventing or controlling pain and anxiety demand a premedication for operations using local anesthesia and for those using sedation or general anesthesia. For optimal patient care, the premedication should be given orally and, with respect to the outpatient basis of the operations, should have a short recovery period. Midazolam, one of the most favored premedications for general anesthesia, has been recommended as a premedication for operations using local anesthesia as well. However, midazolam has only sedative-anxiolytic effects and does not reduce pain sensation, which should be mandatory for operations using local anesthesia. A further requirement is the maintenance of stable hemodynamics for the prevention of postoperative hematomas, especially in the face. For these reasons, another premedication meeting all requirements (anxiolysis, analgesia, and stable hemodynamics) was researched. A randomized, double-blind prospective study was performed from March of 1997 to June of 1998. Five groups totalling 150 patients were included in the study; each group contained 30 patients who had operations performed solely on the face. In the first four groups, the effect of midazolam (0.15 mg/kg(-1)), morphine (0.3 mg/kg(-1)), and clonidine (1.5 microg/kg(-1)) administered orally was compared with a placebo. The fifth group was the control group and received no premedication. To evaluate the effects of the premedications, a corresponding questionnaire was completed independently by the patient and surgeon. With regard to the anxiolytic or analgesic properties of the premedication, 61 percent of the patients preferred pain reduction to anxiety control, and 24 percent of patients preferred reduction of anxiety. The remainder insisted on a reduction of both properties (8 percent) or had no preference (7 percent). Reduction of anxiety was largest in the midazolam and the clonidine groups, but the difference was not significant. The least pain during the application of local anesthesia was experienced by the morphine group (37 percent) and the clonidine group (33 percent), in contrast to the midazolam group (60 percent) (p = 0.04). Morphine and clonidine met the requirements of pain reduction equally well. Nevertheless, considering the rate and intensity of adverse effects with respect to hemodynamic compromises, nausea, and emesis, clonidine is even better suited as an oral premedication for operations on the face using local anesthesia.     

Propofol infusion for sedation in the intensive care unit: preliminary report.

Propofol (2,6,di-isopropylphenol) was given by continuous intravenous infusion to provide sedation after cardiac surgery in 30 patients and its effects compared with those of midazolam given to a further 30 patients. Propofol infusion allowed rapid and accurate control of the level of sedation, which was satisfactory for longer than with midazolam. Patients given propofol recovered significantly more rapidly from their sedation once they had fulfilled the criteria for weaning from artificial ventilation and as a result spent a significantly shorter time attached to a ventilator. There were no serious complications in either group. Both medical and nursing staff considered the propofol infusion to be superior to midazolam in these patients. These findings suggest that propofol is a suitable replacement for etomidate and alphaxalone-alphadolone for sedating patients receiving intensive care.     

Total intravenous anesthesia with midazolam, ketamine, and xylazine or detomidine following induction with tiletamine, zolazepam, and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery

Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean±SD) 1.79±0.29 mg/kg xylazine and 1.79±0.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 69±2 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.5±0.055 mg/kg/hr) and group D, detomidine (2±0.22 μg/kg/hr), both in combination with ketamine (2±0.02 mg/kg/hr) and midazolam (0.03±0.0033 mg/kg/hr), as a constant rate infusion. Anesthesia was reversed with 0.09±0.01 mg/kg atipamezole and 8.7±1.21 μg/kg sarmazenil given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen.     

Contrasting effects of midazolam on induction of heat shock protein 27 by vasopressin and heat in aortic smooth muscle cells.

We previously showed that vasopressin stimulates the induction of heat shock protein (HSP) 27, a low molecular-weight HSP, through protein kinase C activation in aortic smooth muscle A10 cells. In the present study, we examined the effects of midazolam, an intravenous anesthetic, on the HSP27 induction stimulated by vasopressin, heat, or sodium arsenite (arsenite) in A10 cells. Midazolam inhibited the accumulation of HSP27 induced by vasopressin or 12-O-tetradecanoylphorbol 13-acetate (TPA), a direct activator of protein kinase C. Midazolam also reduced the vasopressin-induced level of the mRNA for HSP27. In contrast, midazolam enhanced the HSP27-accumulation induced by heat or arsenite. Midazolam also enhanced the heat-increased level of the mRNA for HSP27. However, midazolam had no effect on the dissociation of the aggregated form of HSP27 following stimulation by vasopressin, heat, or arsenite. These results suggest that midazolam suppresses vasopressin-stimulated HSP27 induction in vascular smooth muscle cells, and that this inhibitory effect is exerted at a point downstream from protein kinase C. In contrast, midazolam enhanced heat- or arsenite-stimulated HSP27 induction. Thus, midazolam has dual effects on the HSP27 induction stimulated by various stresses in vascular smooth muscle cells.     

Comparison of midazolam and diazepam for sedation during plastic surgery

A randomized double-blind study was designed to compare midazolam, a rapid-acting water-soluble benzodiazepine, with diazepam for sedation when administered as an adjuvant to ketamine during local anesthesia. In the preliminary dose-ranging study, midazolam (0.05 to 0.15 mg/kg IV) was found to produce a spectrum of central nervous system activity (e.g., sedation, amnesia) that was similar to diazepam (0.1 to 0.3 mg/kg IV). However, the slope of midazolam's dose-response curve for sedation appeared to be steeper (i.e., a narrower therapeutic dosage range). In a comparative evaluation of their relative sedative-amnestic properties and recovery characteristics, the median effective doses of the two benzodiazepines were compared. Midazolam (0.1 mg/kg IV) was found to produce more profound sedation and amnesia than diazepam (0.2 mg/kg IV). Midazolam was associated with significantly less pain on injection and a lower incidence of postoperative venoirritation. Overall patient acceptance was higher with midazolam compared to diazepam. Finally, recovery characteristics were similar for the two benzodiazepines in our outpatient setting.     

The financial environment of aesthetic surgery: results of a survey of plastic surgeons

To gather information about aesthetic surgery's current practice structures, competitive environment, patient price sensitivity, and marketing and practice development requirements, a two-page survey was developed and mailed to all 1180 members of the American Society for Aesthetic Plastic Surgery. A total of 632 surveys were returned (response rate of 54.5 percent). Most aesthetic plastic surgeons said they were in solo practice (63.3 percent). More than two-thirds described the marketplace as "very competitive," with 59 percent reporting 25 or more surgeons offering aesthetic surgery in their area. They estimated their patients' average income at $62,800. Nearly all plastic surgeons labeled their patients as "moderately price sensitive" (62.3 percent) or "very price sensitive" (30.6 percent). Similarly, 23.2 percent estimated that they had lost 20 or more patients within the last year for reasons of price. Practice development and marketing efforts represented an average of 7.3 percent of plastic surgeons' working time. Parameters associated with a high percentage of time devoted to these activities were solo practice, percentage of revenue from aesthetic surgery greater than 50 percent, a practice environment designation of moderately or very competitive, and ten or more area surgeons offering aesthetic surgery (p < 0.05). High patient income led to only slight decreases in price sensitivity and did not significantly reduce the amount of time spent on marketing and practice development. Although the rest of the healthcare industry has undergone a period of consolidation, aesthetic surgeons have been able to resist these changes. The results of this survey suggest that the fragmented nature of the aesthetic surgery industry is associated with additional burdens on plastic surgeons. As the aesthetic surgery market becomes more competitive, plastic surgeons may benefit from consolidation to reduce costs and maximize efficiency.     

Racial identity,aesthetic surgery and Yorùbá African Values

The question of racial identity in the process and outcome of aesthetic surgery is gaining increasing attention in bioethical discourse. This paper attempts an ethical examination of the racial identity issues involved in aesthetic surgery. Dominant moral values in Western culture are explored in the evaluation of aesthetic surgery. The paper argues that African values are yet to receive the universal attention they arguably deserve especially in the rethinking of values underlying aesthetic surgery as racial transformation. Through a consideration of some moral‐aesthetic values in the Yorùbá‐African culture, this paper further re‐evaluates the ethics of aesthetic surgery. The paper contends against the propagation of aesthetic surgery as a new form of bolstering racial divides and identity in the evolving cosmopolitan age. The position defended in the paper is that some values from Yorùbá‐African culture are useful in the consideration of the ethics of aesthetic surgery and more importantly, in avoiding the racial identity bias embedded in aesthetic surgery. The paper concludes that if due consideration is perhaps given to some African moral‐aesthetic values in the global aesthetic surgery industry, some of the evolving moral and racial complexities would be better mediated.     

Reoxygenation after cold hypoxic storage of cultured precision-cut rat liver slices: effects on cellular metabolism and drug biotransformation.

Cultured rat precision-cut liver slices (PCLS) were used to study the influence of hypothermic preservation and reoxygenation at 37 degrees C on cellular metabolism and drug biotransformation. Cold hypoxic storage caused a depressed metabolism in rat liver slices, but reoxygenation for 8 h at 37 degrees C partially restored the levels of both ATP and GSH and totally restored the capacity to synthesize proteins. Metabolism of midazolam (CYP3A-dependent oxidation) by cold preserved liver slices was decreased by 30% but no further affected by reoxygenation, showing the same profile as freshly cut slices. Such a reoxygenation at 37 degrees C is accompanied by a dramatic loss of CYP3A2 protein while CYP3A1 protein was unaffected. These results suggest that CYP3A2 did not play a major role in midazolam oxidation. Such results are not consistent with a putative reoxygenation injury but rather with cold hypoxic damage. Since cold preserved liver slices did not respond to bacterial endotoxin stimulation (lipopolysaccharides), a minor role of non-parenchymal cells is suggested as mediators for deleterious effects developed during the cold storage.     

Reoxygenation after cold hypoxic storage of cultured precision-cut rat liver slices: effects on cellular metabolism and drug biotransformation

Cultured rat precision-cut liver slices (PCLS) were used to study the influence of hypothermic preservation and reoxygenation at 37°C on cellular metabolism and drug biotransformation. Cold hypoxic storage caused a depressed metabolism in rat liver slices, but reoxygenation for 8 h at 37°C partially restored the levels of both ATP and GSH and totally restored the capacity to synthesize proteins. Metabolism of midazolam (CYP3A-dependent oxidation) by cold preserved liver slices was decreased by 30% but no further affected by reoxygenation, showing the same profile as freshly cut slices. Such a reoxygenation at 37°C is accompanied by a dramatic loss of CYP3A2 protein while CYP3A1 protein was unaffected. These results suggest that CYP3A2 did not play a major role in midazolam oxidation. Such results are not consistent with a putative reoxygenation injury but rather with cold hypoxic damage. Since cold preserved liver slices did not respond to bacterial endotoxin stimulation (lipopolysaccharides), a minor role of non-parenchymal cells is suggested as mediators for deleterious effects developed during the cold storage.     

Effects of an anesthetic mixture of medetomidine,midazolam, and butorphanol in rats—strain difference and antagonism by atipamezole

An anesthetic mixture of medetomidine (MED), midazolam (MID), and butorphanol (BUT) has been used in laboratory animals. We previously reported that this anesthetic mixture produced closely similar anesthetic effects in BALB/c and C57BL/6J strains. We also demonstrated the efficacy of atipamezole (ATI), an antagonist of MED that produced quick recovery from anesthesia in mice. Anesthetics have various anesthetic effects among animal strains. However, the differences in the effects of anesthetic mixtures in rats are unclear. In the present study, we first examined effects of the abovementioned anesthetic mixture using three different rat strains: Wistar (WST), Sprague-Dawley (SD), and Fischer 344 (F344). Second, we examined how different dosages and optimum injection timing of ATI affected recovery from anesthesia in rats. We used the anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs. We found no significant differences in anesthetic duration among the three different strains. However, recovery from anesthesia in the SD strain took significantly longer than in the other strains. The antagonistic effects of ATI (0.15 mg/kg and 0.75 mg/kg) were equivalent when administered at 30 min after anesthetic mixture administration. The antagonistic effects of ATI 0.75 mg/kg were stronger than those of ATI 0.15 mg/kg at 10 min after anesthetic mixture administration. This anesthetic mixture is a useful drug that can induce similar anesthetic effects in three different strains and has an antagonist, ATI, that makes rats quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.     

The Anxiolytic Effect of Midazolam in Third Molar Extraction: A Systematic Review

Purpose

To assess the efficacy of midazolam for anxiety control in third molar extraction surgery.

Methods

Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team.

Results

Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone.

Conclusion

It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient’s respiratory function must be monitored closely, because multidrug sedation is also more risky.