Monoamine oxidase A inhibitor-near-infrared dye conjugate reduces prostate tumor growth.

Development of anti-cancer agents with high tumor-targeting specificity and efficacy is critical for modern multidisciplinary cancer research. Monoamine oxidase A (MAOA), a mitochondria-bound enzyme, degrades monoamine neurotransmitters and dietary monoamines. Recent evidence suggests a correlation between increased MAOA expression and prostate cancer (PCa) progression with poor outcomes for patients. MAOA induces epithelial-mesenchymal transition (EMT) and augments hypoxic effects by producing excess reactive oxygen species. Thus, development of MAOA inhibitors which selectively target tumors becomes an important goal in cancer pharmacology. Here we describe the design, synthesis, and in vitro and in vivo evaluation of NMI, a conjugate that combines a near-infrared dye for tumor targeting with the moiety derived from the MAOA inhibitor clorgyline. NMI inhibits MAOA with low micromolar IC50, suppresses PCa cell proliferation and colony formation, and reduces migration and invasion. In mouse PCa xenografts, NMI targets tumors with no detectable accumulation in normal tissues, providing effective reduction of the tumor burden. Analysis of tumor specimens shows reduction in Ki-67(+) and CD31(+) cells, suggesting a decrease of cell proliferation and angiogenesis and an increase in M30(+) cells, indicating increased apoptosis. Gene expression profiles of tumors treated with NMI demonstrate reduced expression of oncogenes FOS, JUN, NFKB, and MYC and cell cycle regulators CCND1, CCNE1, and CDK4/6, along with increases in the levels of tumor suppressor gene TP53, cell cycle inhibitors CDKN1A and CDKN2A, and MAOA-downstream genes that promote EMT, tumor hypoxia, cancer cell migration, and invasion. These data suggest that NMI exerts its effect through tumor-targeted delivery of a MAOA-inactivating group, making NMI a valuable anti-tumor agent.

Reduction in intraoperative bacterial contamination of peripheral intravenous tubing through the use of a passive catheter care system.

BACKGROUND: Bacterial contamination of intravascular devices has been associated with increased morbidity and mortality in various hospital settings, including the perioperative environment. Catheter hub disinfection has been shown in an ex vivo model to attenuate intraoperative injection of bacterial organisms originating from the anesthesia provider's hands, providing the impetus for improvement in intraoperative disinfection techniques and compliance. In the current study, we investigated the clinical effectiveness of a new, passive catheter care station in reducing the incidence of bacterial contamination of open lumen patient IV stopcock sets. The secondary aim was to evaluate the impact of this novel intervention on the combined incidence of 30-day postoperative infections and IV catheter-associated phlebitis. METHODS: Five hundred ninety-four operating room environments were randomized by a computer-generated list to receive either a novel catheter care bundle (HubScrub and DOCit) or standard caps in conjunction with a sterile, conventional open lumen 3-way stopcock set (24 inch with 3-gang 4-way and T-Connector). Patients underwent general anesthesia according to usual practice and were followed prospectively for 30 postoperative days to identify the development of health care-associated infections (HCAIs) and/or phlebitis. The primary outcome was intraoperative bacterial contamination of the primary stopcock set used by the anesthesia provider(s). The secondary outcome was the combined incidence of 30-day postoperative infections and phlebitis. RESULTS: Five hundred seventy-two operating rooms were included in the final analysis. Study groups were comparable with no significant differences in patient, provider, anesthetic, or procedural characteristics. The catheter care station reduced the incidence of primary stopcock lumen contamination compared with standard caps (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.63-0.98, P = 0.034) and was associated with a reduction in the combined incidence of HCAIs and IV catheter-associated phlebitis with and without adjustment for patient and procedural covariates (OR(adjusted) 0.589, 95% CI 0.353-0.984, P = 0.040). The risk-adjusted number needed to treat to eliminate 1 case of lumen contamination was 9 (95% CI 3.4-13.5) patients, whereas the risk-adjusted number needed to treat to eliminate 1 case of HCAI/catheter-associated phlebitis was 17 (95% CI 11.8-17.9) patients. CONCLUSION: Intraoperative use of a passive catheter care station significantly reduced open lumen bacterial contamination and the combined incidence of 30-day postoperative infections and phlebitis.

Prevention of intravenous bacterial injection from health care provider hands: the importance of catheter design and handling.

BACKGROUND: Device-related bloodstream infections are associated with a significant increase in patient morbidity and mortality in multiple health care settings. Recently, intraoperative bacterial contamination of conventional open-lumen 3-way stopcock sets has been shown to be associated with increased patient mortality. Intraoperative use of disinfectable, needleless closed catheter devices (DNCCs) may reduce the risk of bacterial injection as compared to conventional open-lumen devices due to an intrinsic barrier to bacterial entry associated with valve design and/or the capacity for surface disinfection. However, the relative benefit of DNCC valve design (intrinsic barrier capacity) as compared to surface disinfection in attenuation of bacterial injection in the clinical environment is untested and entirely unknown. The primary aim of the current study was to investigate the relative efficacy of a novel disinfectable stopcock, the Ultraport zero, with and without disinfection in attenuating intraoperative injection of potential bacterial pathogens as compared to a conventional open-lumen stopcock intravascular device. The secondary aims were to identify risk factors for bacterial injection and to estimate the quantity of bacterial organisms injected during catheter handling. METHODS: Four hundred sixty-eight operating room environments were randomized by a computer generated list to 1 of 3 device-injection schemes: (1) injection of the Ultraport zero stopcock with hub disinfection before injection, (2) injection of the Ultraport zero stopcock without prior hub disinfection, and (3) injection of the conventional open-lumen stopcock closed with sterile caps according to usual practice. After induction of general anesthesia, the primary anesthesia provider caring for patients in each operating room environment was asked to perform a series of 5 injections of sterile saline through the assigned device into an ex vivo catheter system. The primary outcome was the incidence of bacterial contamination of the injected fluid column (effluent). Risk factors for effluent contamination were identified in univariate analysis, and a controlled laboratory experiment was used to generate an estimate of the bacterial load injected for contaminated effluent samples. RESULTS: The incidence of effluent bacterial contamination was 0% (0/152) for the Ultraport zero stopcock with hub disinfection before injection, 4% (7/162) for the Ultraport zero stopcock without hub disinfection before injection, and 3.2% (5/154) for the conventional open-lumen stopcock. The Ultraport zero stopcock with hub disinfection before injection was associated with a significant reduction in the risk of bacterial injection as compared to the conventional open-lumen stopcock (RR = 8.15 × 10(-8), 95% CI, 3.39 × 10(-8) to 1.96 × 10(-7), P = <0.001), with an absolute risk reduction of 3.2% (95% CI, 0.5% to 7.4%). Provider glove use was a risk factor for effluent contamination (RR = 10.48, 95% CI, 3.16 to 34.80, P < 0.001). The estimated quantity of bacteria injected reached a clinically significant threshold of 50,000 colony-forming units per each injection series. CONCLUSIONS: The Ultraport zero stopcock with hub disinfection before injection was associated with a significant reduction in the risk of inadvertent bacterial injection as compared to the conventional open-lumen stopcock. Future studies should examine strategies designed to facilitate health care provider DNCC hub disinfection and proper device handling.

The use of intraoperative ultrasound by anesthesiologists to facilitate the surgical management of peripheral nerve tumors of the upper extremity.

BACKGROUND: Traditional uses of ultrasound by anesthesiologists include transesophageal echocardiography, facilitation of vascular access, and guidance of peripheral nerve blocks. METHODS: In this case series, we report a novel application of ultrasound by anesthesiologists to facilitate the operative dissection of upper extremity peripheral nerve tumors. RESULTS: In four cases, ultrasound was used to intraoperatively locate the tumor, plan the safest surgical approach, and exclude tumor vascularity. CONCLUSIONS: Ultrasound can be used by anesthesiologists to facilitate the surgical management of peripheral nerve tumors.

Characterizing novice behavior associated with learning ultrasound-guided peripheral regional anesthesia.

BACKGROUND AND OBJECTIVES: Ultrasound-guided regional anesthesia is a rapidly growing field. There exists little information regarding the competencies involved with such a practice. The objective of this exploratory study was to characterize the behavior of novices as they undertook the challenges of learning a new technique. In addition to assessing for both committed errors and accuracy, we aimed to identify previously unrecognized quality-compromising behaviors that could help structure effective training interventions. METHODS: By using detailed video analyses, the performances of 6 anesthesia residents were evaluated while on a dedicated 1-month rotation in ultrasound-guided regional anesthesia. From these video reviews, we assessed accuracy, errors committed, performance times, and searched for previously unrecognized quality-compromising behaviors. RESULTS: A total of 520 nerve blocks were videotaped and reviewed. All residents performed at least 66 nerve blocks, with an overall success rate of 93.6% and 4 complications. Both speed and accuracy improved throughout the rotation. There were a total of 398 errors committed, with the 2 most common errors consisting of the failure to visualize the needle before advancement and unintentional probe movement. Five quality-compromising patterns of behavior were identified: (1) failure to recognize the maldistribution of local anesthesia, (2) failure to recognize an intramuscular location of the needle tip before injection, (3) fatigue, (4) failure to correctly correlate the sidedness of the patient with the sidedness of the ultrasound image, and (5) poor choice of needle-insertion site and angle with respect to the probe preventing accurate needle visualization. CONCLUSIONS: Based on the analysis of the committed errors and the identification of quality-compromising behaviors, we are able to recommend important targets for learning in future training and simulation programs.

An abnormal clinical course of an ultrasound-guided supraclavicular brachial plexus block using 0.375% bupivacaine.

We report on the case of a reappearance of a supraclavicular nerve block after the apparent initiation of its resolution in a 21-year-old athlete undergoing repair of a valgus impaction syndrome of his right elbow. The patient's anesthetic management consisted of a supraclavicular nerve block and general anesthesia. The patient was discharged home with an apparent resolving nerve block. He returned to the hospital urgently when, at 7 hours after blockade, he lost all motor-sensory function in his arm. His workup ultimately yielded negative results, and the block resolved at 23 hours. In addition to documenting an abnormal course of a supraclavicular block, this case report questions the appropriateness of placing long-acting nerve blocks in outpatients.

Use of a nerve stimulator does not improve the efficacy of ultrasound-guided supraclavicular nerve blocks.

OBJECTIVE: To evaluate the efficacy of nerve stimulation as an adjunct to ultrasound-guided supraclavicular nerve blocks. DESIGN: Prospective database review. SETTING: Tertiary-care medical center. MEASUREMENTS: The records of 94 consecutive adult patients requiring surgery below the elbow and consenting to receive regional anesthesia were studied. The focus of this study was on supraclavicular nerve block using ultrasound guidance for nerve identification and needle localization. A nerve stimulator with a motor response lower than 0.5 mA was used for confirmation of findings. An ultrasound image was considered adequate if two trunks of the brachial plexus were visualized and if the needle was completely seen on the long axis. A successful block was defined as one that sufficed as the sole anesthetic without conversion to general anesthesia. Motor and sensory examination findings on the upper extremity were also evaluated. RESULTS: 74 patients had an adequate ultrasound image. Of the 64 patients with a positive motor response, 88% had a successful block, as compared with 90% of the 10 patients without a motor response (relative risk, 1.09; 95% confidence interval, 0.79-1.51; P = 0.52). Neither multivariate correction for baseline characteristics nor inclusion of the 20 patients with inadequate ultrasound images changed the results. CONCLUSION: For adequately imaged ultrasound-guided supraclavicular nerve blocks, a positive motor response to nerve stimulation does not increase the success rate of the block. In addition, the high false-negative rate suggests that these blocks are usually effective, even in the absence of a motor response. Nerve stimulation as an adjunct to ultrasound guidance may have a limited role.

The use of magnetic resonance imaging to evaluate the accuracy of a handheld ultrasound machine in localizing the sciatic nerve in the popliteal fossa.

BACKGROUND AND OBJECTIVE: Ultrasound has become an increasingly popular modality in facilitating the performance of peripheral nerve blocks. There is a paucity of data describing techniques of ultrasound-guided sciatic nerve blocks. By using magnetic resonance imaging (MRI) as a gold standard, the objective of this study was to describe the ability of a handheld ultrasound machine to accurately locate the sciatic nerve. METHODS: Ten patients were prospectively enrolled and placed in the prone position. By using a 4- to 7-MHz ultrasound transducer, the sciatic nerve was visualized in short axis between 5 to 10 cm above the popliteal crease. The distance from the skin to the nerve was measured by ultrasound, and a MRI lucent marker was placed at this site. This process was repeated in one additional location. The patient was then placed supine in the MRI scanner and short-axis T1-weighted images were obtained. On the MRI image, we recreated the 2 lines extending down from the markers using the distances previously measured by ultrasound. The point of intersection of these 2 lines represents the ultrasound-determined location of the sciatic nerve, which was then compared with the midpoint of the nerve complex on MRI. RESULTS: The sciatic nerve was easily visualized by ultrasound in all 10 patients. MRI showed the division of the sciatic nerve in 9 out of 10 patients. Ultrasound was able to confirm this division in 7 patients. The mean distance between the MRI and ultrasound midpoint location of the sciatic nerve was 2.9 +/- 1.3 mm. CONCLUSIONS: The data presented here suggest that the specific ultrasound machine evaluated in this study can accurately localize the sciatic nerve in the popliteal fossa.

The learning curve associated with a simulated ultrasound-guided interventional task by inexperienced anesthesia residents.

BACKGROUND AND OBJECTIVE: Ultrasound has become an increasingly popular modality in facilitating the performance of peripheral nerve blocks. There exists no literature that examines the learning curve of the ultrasound novice. In this prospective series, we evaluated the learning curve of inexperienced anesthesia residents in performing a simulated ultrasound-guided interventional procedure. In doing so, we hoped to identify reproducible patterns of human errors, which could potentially aid in the prevention of real-life iatrogenic injuries. METHODS: Ten subjects were prospectively enrolled. After a brief introduction to the ultrasound system, the subjects were asked to perform 6 sequential trials of a simulated breast cyst aspiration. For the first 3 trials, each subject attempted to place a 22-gauge b-bevel needle into any aspect of an olive buried inside the turkey breast. After completion of these 3 trials, the subjects were asked to place the needle into the exact midpoint of the olive wall closest to the transducer. Trials were videotaped and analyzed for task performance in terms of speed and accuracy. RESULTS: All subjects successfully completed the 6 interventional trials. The mean time to perform the task was reduced by 38% and 48%, respectively, for the second and third trials. A composite score of accuracy showed an improvement of 36% and 59%, respectively, for the second and third trials. The most common committed error, which occurred in 7 of 10 subjects, was the failure to accurately image the needle while advancing. This resulted in excessive depth of penetration and inadvertent transfixation of the olive in 5 of these subjects. CONCLUSIONS: Anesthesiology residents, with little or no ultrasound experience, can rapidly learn and improve their speed and accuracy in performing a simulated interventional ultrasound procedure. A concerning novice pattern was identified where the subjects advanced the needle even though it was not appropriately visualized in the ultrasound beam. This resulted in needle placement error, which could cause iatrogenic injury in the clinical setting.

A selective mitochondrial-targeted chlorambucil with remarkable cytotoxicity in breast and pancreatic cancers.

Nitrogen mustards, widely used as chemotherapeutics, have limited safety and efficacy. Mitochondria lack a functional nucleotide excision repair mechanism to repair DNA adducts and are sensitive to alkylating agents. Importantly, cancer cells have higher intrinsic mitochondrial membrane potential (Δψmt) than normal cells. Therefore, selectively targeting nitrogen mustards to cancer cell mitochondria based on Δψmt could overcome those limitations. Herein, we describe the design, synthesis, and evaluation of Mito-Chlor, a triphenylphosphonium derivative of the nitrogen mustard chlorambucil. We show that Mito-Chlor localizes to cancer cell mitochondria where it acts on mtDNA to arrest cell cycle and induce cell death, resulting in a 80-fold enhancement of cell kill in a panel of breast and pancreatic cancer cell lines that are insensitive to the parent drug. Significantly, Mito-Chlor delayed tumor progression in a mouse xenograft model of human pancreatic cancer. This is a first example of repurposing chlorambucil, a drug not used in breast and pancreatic cancer treatment, as a novel drug candidate for these diseases.

Spinal anesthesia for orthopedic surgery: a detailed video assessment of quality.

BACKGROUND: Subarachnoid blocks are considered routine anesthetic procedures important in the daily practices of most anesthesiologists. However, few data exist regarding modern failure rates or quality-compromising behaviors. METHODS: Sixty adult patients having orthopedic surgery under spinal anesthesia were enrolled in this prospective and observational video study. Through a detailed high definition video review, we aimed to define our subarachnoid block failure rate and identify associated quality-compromising behaviors. RESULTS: An intrathecal injection either failed to generate a surgical block or was aborted secondary to difficulty in 7 patients (11.6%). A procedurally difficult subarachnoid block occurred in 17 patients (29%). Eight patients required greater than 10 mins of needling to complete the subarachnoid block. Body mass index represented an independent risk factor for long procedure times. There were 27 incidences of quality-compromising behaviors that included likely violation of aseptic technique, hemorrhage, poor positioning, damaged needles, thecal sac transfixation, high-lumbar needle placement, repetition of previously failed maneuvers, failure to provide skin anesthesia, and prolonged procedure times. Certified registered nurse anesthetist status predicted a greater-than-4-fold risk of subarachnoid block failure. DISCUSSION: The failure rate and quality-compromising behaviors identified in this study challenge the generalized assumption that performing a subarachnoid block in the orthopedic population is a simple procedure. The number and nature of the combined failed and difficult subarachnoid blocks suggest the need for quality improvement. Further research is needed to assess whether the use of image guidance may be a possible solution to navigate difficult anatomical pathology and confirm correct needle and drug placement.

Postoperative hemodynamic instability after simultaneous bilateral total knee arthroplasty.

OBJECTIVES: After a simultaneously performed bilateral total knee arthroplasty, our institutional clinical experience suggested that there was an alarming incidence of severe postoperative hypotension and bradycardia. We therefore performed this study to define the incidence of postoperative hemodynamic instability and identify associated risk factors. METHODS: This study involved a retrospective review of 312 consecutive patients undergoing bilateral total knee arthroplasty. The primary outcome was a hypotensive event in the postoperative period. This was defined as a systolic blood pressure of less than 85 mm Hg and/or the need for emergency postoperative medical management. Logistic regression was used to estimate odds ratios. RESULTS: The incidence of hypotensive events in the postanesthesia care unit was 17% (95% confidence interval [CI], 13%-22%). The incidence of simultaneous hypotension and bradycardia was 7% (95% CI, 4%-10%). Of all patients, 10% required emergent treatment with vasopressors or vagolytics (95% CI, 7%-13%). The performance of the operation under spinal anesthesia was an independent risk factor (odds ratio = 4.5, P < 0.01) for the development of postoperative hypotension (21%) compared with general anesthesia (5.7%). Spinal anesthesia continued to predict hypotension in multivariate modeling that controlled for confounding variables. CONCLUSIONS: Hypotension was common after bilateral total knee replacement in our series. Performance of the operation under spinal anesthesia was a significant risk factor for the development of postoperative hypotension compared with general anesthesia. General anesthesia may offer a greater margin of postoperative hemodynamic stability and perhaps safety for patients undergoing this procedure.

A comparison of sensory and motor loss after a femoral nerve block conducted with ultrasound versus ultrasound and nerve stimulation.

BACKGROUND: Controversy exists regarding the need for nerve stimulation when performing an ultrasound (US)-guided peripheral nerve block. We tested the hypothesis that the quality of a femoral nerve block (FNB) performed with US is equivalent to an FNB performed with US and nerve stimulation. METHODS: One hundred seven patients undergoing unilateral total knee arthroplasty were randomized to receive either a US-guided FNB (group US) or a US-guided FNB with nerve stimulation (group USNS). Thirty milliliters of bupivacaine 0.5% was injected in both groups. At 10, 20, 30, and 40 mins after block placement, blinded motor and sensory examinations were conducted. Secondary outcomes included time to perform the block, the number of needle redirections, and 24-hrs intravenously administered morphine equivalent consumption. RESULTS: There were no significant differences in the proportion of patients with either a partial or complete block. At 40 mins, 95.7% of the USNS subjects had a partial or complete sensory block of the femoral nerve (complete in 71.7% and partial in 24%) compared with 88.1% of US subjects (complete in 69% and partial in 19.1%; odds ratio, 2.97; P = 0.19). There were more needle redirections in group USNS (4.1 vs 1.1, P < 0.001), with a higher percentage of patients requiring 2 or more needle attempts (44.2% vs 18.9%, P < 0.01). The time to perform the block in group USNS was longer (188 vs 148 secs, P = 0.01). CONCLUSION: The addition of nerve stimulation to a US-guided FNB did not change preoperative block efficacy.

Ultrasound improves the success rate of a sural nerve block at the ankle.

BACKGROUND AND OBJECTIVES: : During ankle block performance, anesthetizing the sural nerve is important for generating complete anesthesia of the lateral aspect of the foot. We hypothesized that an ultrasound-guided perivascular approach, utilizing the lesser saphenous vein as a reference, would prove more successful than a conventional approach based on surface landmarks. METHODS: : Eighteen healthy volunteers were prospectively randomized into this controlled and blinded study. Each subject was placed prone and the right ankle was randomized to receive either an ultrasound-guided perivascular sural nerve block (group US) or a traditional landmark-based sural nerve block (group TRAD). The subject's left ankle then received the alternate approach. The ultrasound technique relied on injecting local anesthetic circumferentially around the lesser saphenous vein. All blocks were performed with 5 mL of 3% chloroprocaine. We evaluated sensory block to ice and pinprick. Secondary outcome variables included performance times, number of needle passes, participant satisfaction, and presence of any complications. RESULTS: : At the midfoot position, testing at 10 minutes after block placement revealed a loss of sensation to ice in 94% (complete in 78% and partial in 16%) in the US group versus 56% in the TRAD group (complete in 28%, partial in 28%) (P <.01). Complete loss of sensation to ice persisted in 33% of the US group as compared with 6% in the TRAD group at 60 minutes (P <.05). A similar pattern was observed when the blocks were tested with pinprick. Ultrasound-guided blocks took longer to perform on average than the traditional blocks (mean difference of 102 seconds, P <.001). The ultrasound block was subjectively felt to be denser by 88% of the subjects (P =.001). CONCLUSIONS: : Ultrasound guidance using the lesser saphenous vein as a reference point results in a more complete and longer lasting sural nerve block than does a traditional approach using surface landmarks.

Enantioselective total synthesis of avrainvillamide and the stephacidins.

In this article, full details regarding our total synthesis of avrainvillamide and the stephacidins are presented. After an introduction and summary of prior synthetic studies in this family of structurally complex anticancer natural products, the evolution of a final synthetic approach is described. Thus, a thorough description of three separate model studies is provided for construction of the characteristic bicyclo[2.2.2]diazaoctane ring system common to these alkaloids. The first and second approaches sought to build the core using formal Diels-Alder and vinyl radical pathways, respectively. Although these strategies failed in their primary objective, they fostered the development of a new and mechanistically intriguing method for the synthesis of indolic enamides such as those found in numerous bioactive natural products. The scope and generality of this simple method for the direct dehydrogenation of tryptophan derivatives is described. Finally, details of a third and successful route to the core of these alkaloids are described which features oxidative C-C bond formation. Specifically, the first heterocoupling of two different types of carbonyl species (ester and amide) is accomplished in good yield, on a preparative scale, and with complete stereocontrol. The information gained in these model studies enabled an enantioselective total synthesis of stephacidin A. The absolute configuration of these alkaloids was firmly established in collaboration with Professor William Fenical. A full account of our successful efforts to convert stephacidin A into stephacidin B via avrainvillamide is presented. Finally, the first analogues of these natural products have been prepared and evaluated for anticancer activity.

A single injection ultrasound-assisted femoral nerve block provides side effect-sparing analgesia when compared with intrathecal morphine in patients undergoing total knee arthroplasty.

Postoperative pain after total knee arthroplasty (TKA) is severe, and achieving adequate analgesia remains a clinical challenge. We tested the hypothesis that, in patients having unilateral TKA under intrathecal (IT) anesthesia, the addition of a femoral nerve block would provide superior analgesia when compared with IT morphine and demonstrate fewer adverse side effects. In a single-blinded and controlled trial, 41 ASA I-III patients undergoing unilateral TKA were randomized into 2 groups. Both groups received 15 mg of IT hyperbaric bupivacaine for the surgical anesthetic. Group ITM received 250 microg of IT morphine and group FNB received an ultrasound-assisted femoral nerve block with 40 mL of 0.5% ropivacaine, 5 microg/mL of epinephrine, and 75 microg of clonidine. At 1, 2, 4, 6, 12, and 24 h postoperatively, we measured visual analog scales for pain, cumulative IV morphine consumption, hemodynamics, and side effects. There were no statistically significant differences in morphine consumption, pain at rest, or pain with movement. However, group FNB had fewer perioperative side effects including nausea, vomiting, and pruritus (P < 0.05 for each event). This corresponded to a decrease in patient satisfaction in group ITM, in which 20% of the patients rated their experience as "unsatisfactory" (P < 0.05). We conclude that, in comparison with IT morphine, a single injection femoral nerve block provides equivalent analgesia but with a significant reduction in side effects for patients having TKA under bupivacaine intrathecal anesthesia.