A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study.

INTRODUCTION: Erythropoiesis-stimulating agents, standard of care for anemia of end-stage kidney disease, are associated with cardiovascular events. We evaluated the efficacy and safety of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. METHODS: SIERRAS was a phase 3, randomized, open-label, active-controlled study enrolled adults on dialysis for end-stage kidney disease receiving erythropoiesis-stimulating agents for anemia. Patients were randomized (1:1) to thrice-weekly roxadustat or epoetin alfa. Doses were based on previous epoetin alfa dose and adjusted in the roxadustat arm to maintain hemoglobin at ∼11 g/dl during treatment. Epoetin alfa dosing was adjusted per US package insert. Primary efficacy endpoint was mean hemoglobin (g/dl) change from baseline averaged over weeks 28 to 52. Treatment-emergent adverse events were monitored. RESULTS: Enrolled patients (roxadustat, n = 370 and epoetin alfa, n = 371) had similar mean (SD) baseline hemoglobin levels (10.30 [0.66] g/dl). Mean (SD) hemoglobin changes for weeks 28 to 52 were 0.39 (0.93) and -0.09 (0.84) in roxadustat and epoetin alfa, respectively. Roxadustat was noninferior (least squares mean difference: 0.48 [95% confidence interval: 0.37, 0.59]; P < 0.001) to epoetin alfa. Tolerability was comparable between treatments. CONCLUSION: In end-stage kidney disease, roxadustat was noninferior to epoetin alfa in up to 52 weeks of treatment in this erythropoietin-stimulating agent conversion study. Roxadustat had an acceptable tolerability profile.

Roxadustat for CKD-related Anemia in Non-dialysis Patients.

INTRODUCTION: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis. METHODS: ANDES was a global Phase 3 randomized study in which adults with stage 3-5 CKD not on dialysis received roxadustat or placebo. Patients were initially dosed thrice weekly; dose was titrated to achieve a hemoglobin level ≥11.0 g/dl, followed by titration for maintenance. The primary endpoints were change in hemoglobin (weeks 28-52) and proportion of patients achieving a hemoglobin response (hemoglobin ≥11.0 g/dl and increase ≥1.0 g/dl [baseline >8.0 g/dl], or increase ≥2.0 g/dl [baseline ≤8.0 g/dl]) (week 24). Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were recorded. RESULTS: In roxadustat (n = 616) and placebo (n = 306) groups, hemoglobin mean (SD) change from baseline over weeks 28-52 was significantly larger for roxadustat (2.00 [0.95]) versus placebo (0.16 [0.90]), corresponding to least-squares mean difference of 1.85 g/dl (95% confidence interval [CI] 1.74-1.97; P < 0.0001). The proportion of patients achieving a response at week 24 was larger for roxadustat (86.0%; 95% CI 83.0%-88.7%) versus placebo (6.6%; 95% CI 4.1%-9.9%; P < 0.0001). The proportion of patients receiving rescue therapy at week 52 was smaller for roxadustat (8.9%) versus placebo (28.9%); hazard ratio, 0.19 (95% CI 0.14-0.28; P < .0001). The incidences of TEAEs and TESAEs were comparable. CONCLUSION: This study showed that roxadustat corrected and maintained hemoglobin and was well tolerated in patients with CKD-related anemia not on dialysis (ClinicalTrials.gov NCT01750190).

[Paraspinous Sagittal Shift (PSSS): a novel approach for transmuscular quadratus lumborum block for hip surgery analgesia - four case reports]. / Paraespinhoso Sagital (PES): nova técnica no bloqueio transmuscular do quadrado lombar para analgesia em cirurgia de quadril ­ relato de quatro casos.

BACKGROUND: Effective pain management is essential for successful rehabilitation and enhanced recovery after joint arthroplasty. The Quadratus Lumborum Block (QLB) has mostly been described for abdominal surgery, but has also recently been applied to hip surgery patients. METHODS: In the following cases series, we suggest a modification of the TQL block described as Paraspinous Sagittal Shift QL block. We hypothesize that this approach may allow better LA spread to the lumbar nerve roots. Such technique involves a craniocaudal approach of LA injection between the QL and PM muscles behind the Anterior Thoracolumbar Fascia (ATLF) at the level of L4. Cases were provided with combined GA and PSSS modification of QL block via a single shot or catheter technique. RESULTS: Sensory distribution of the block in the four patients studied was found to cover the area between the T11-12 and L4-5 dermatomes. Spread of the injectate was confirmed via an A-P fluoroscopy imaging of the lumbosacral spine after injection of a mixture of LA and a contrast in the plane between the QL and PM muscles in two cases. CONCLUSIONS: The PSSS technique for TQL block may be beneficial as a part of multimodal analgesia for hip surgeries. This technique may be a safe alternative to psoas compartment block; however, future comparative studies are recommended. The PSSS technique for TQL block also may provide an easy access for catheter insertion.

Paraspinous Sagittal Shift (PSSS): a novel approach for transmuscular quadratus lumborum block for hip surgery analgesia - four cases report / Paraespinhoso Sagital (PES): nova técnica no bloqueio transmuscular do quadrado lombar para analgesia em cirurgia de quadril - relato de quatro casos

Abstract Background: Effective pain management is essential for successful rehabilitation and enhanced recovery after joint arthroplasty. The Quadratus Lumborum Block (QLB) has mostly been described for abdominal surgery, but has also recently been applied to hip surgery patients. Methods: In the following cases series, we suggest a modification of the TQL block described as Paraspinous Sagittal Shift QL block. We hypothesize that this approach may allow better LA spread to the lumbar nerve roots. Such technique involves a craniocaudal approach of LA injection between the QL and PM muscles behind the Anterior Thoracolumbar Fascia (ATLF) at the level of L4. Cases were provided with combined GA and PSSS modification of QL block via a single shot or catheter technique. Results: Sensory distribution of the block in the four patients studied was found to cover the area between the T11-12 and L4-5 dermatomes. Spread of the injectate was confirmed via an A-P fluoroscopy imaging of the lumbosacral spine after injection of a mixture of LA and a contrast in the plane between the QL and PM muscles in two cases. Conclusions: The PSSS technique for TQL block may be beneficial as a part of multimodal analgesia for hip surgeries. This technique may be a safe alternative to psoas compartment block; however, future comparative studies are recommended. The PSSS technique for TQL block also may provide an easy access for catheter insertion.

Resumo Justificativa: O controle efetivo da dor é essencial para a reabilitação bem-sucedida e melhor recuperação após artroplastia. O bloqueio do quadrado lombar tem sido descrito principalmente para cirurgia abdominal, mas recentemente também tem sido usado para pacientes submetidos a cirurgia de quadril. Método: Na série de casos a seguir, sugerimos modificação na técnica do bloqueio transmuscular do quadrado lombar descrita como bloqueio do Quadrado Lombar Paraespinhoso Sagital (PES). Nossa hipótese é de que a técnica permitiria melhor dispersão do anestésico local para as raízes dos nervos lombares. Tal técnica envolve acesso craniocaudal para injeção do anestésico local entre os músculos quadrado lombar e psoas maior atrás da Fáscia Toracolombar Anterior (FTLA) no nível de L4. Os casos foram submetidos a anestesia geral combinada a técnica modificada PES para bloqueio do quadrado lombar via injeção única ou cateter. Resultados: Verificou-se que a distribuição sensorial do bloqueio nos quatro pacientes estudados cobriu a área entre os dermátomos T11-12 e L4-5. A dispersão do anestésico injetado foi confirmada via fluoroscopia A-P da coluna lombo-sacral após injeção, em dois casos, de solução de anestésico local e contraste no plano entre os músculos quadrado lombar e psoas maior. Conclusões: A técnica PES para bloqueio transmuscular do quadrado lombar pode ser benéfica como componente da analgesia multimodal para cirurgias de quadril. A técnica pode ser alternativa segura para bloqueio do compartimento psoas; entretanto, estudos comparativos futuros são recomendados. A técnica PES para bloqueio transmuscular do quadrado lombar pode também fornecer acesso fácil para inserção do cateter.

Erector spinae versus paravertebral plane blocks in modified radical mastectomy: Randomised comparative study of the technique success rate among novice anaesthesiologists.

BACKGROUND AND AIMS: Regional analgesia may play a role in pain management during breast surgery. Ultrasound approach to paravertebral block may be challenging. This study compared success rates of ultrasound-guided erector spinae plane block (ESPB) versus parasagittal in-plane thoracic paravertebral block among senior anaesthesia residents in modified radical mastectomy. METHODS: One hundred and two female patients undergoing modified radical mastectomy were randomly categorized into PARA group receiving sagittal in-plane paravertebral block and ESPB group receiving erector spinae plane block. The block in the 1st six cases in each group was done by an experienced consultant as a demonstration for three anaesthesia residents not experienced in either block. Primary endpoint was assessing success rate of the blocks. Secondary endpoint was the haemodynamic response to skin incision and postoperative analgesia. RESULTS: All patients were females undergoing modified radical mastectomy. Success rate among residents was 100% in ESPB versus 77.8% in PARA group (P = 0.002). Duration to perform the block was less in ESPB group (4.39 ± 1.2 min) than PARA group (8.18 ± 2.42 min) (P < 0.0001). Guidance frequency by consultants was significantly higher in PARA than ESPB group. Time to 1st analgesic requirement and morphine consumption postoperatively were insignificant between the groups. There was no significant difference regarding haemodynamics. CONCLUSION: ESPB may be a simple and safe alternative to parasagittal in-plane paravertebral block to provide postoperative analgesia in modified radical mastectomy especially in novice practitioners. It provides equivalent profile of postoperative analgesia with less time to perform the block.

Clinical outcomes associated with the use of the NexSite hemodialysis catheter with new exit barrier technology: Results from a prospective, observational multi-center registry study.

PURPOSE: Decreasing the risk of catheter related bloodstream infections (CRBSIs) remains a key focus for improving outcomes and reducing cost of care for hemodialysis (HD) patients. Recent studies demonstrate CRBSI rates can be improved by managing bacterial colonization at the catheter exit site. Herein we present the results of a study documenting the clinical performance of the NexSite HD catheter, a new tunneled central venous catheter which incorporates Exit Site Management (ESM) technology. METHODS: We conducted an observational study using a prospective, multi-center registry of HD patients implanted with the NexSite HD catheter. The primary endpoint for the study was CRBSI rate for a period up to 180-days following catheter placement. Secondary endpoints included device placement success rate, exit site healing, development of an exit site or tunnel infection, and early or late non-infectious catheter-related complications. All reasons for early non-elective catheter removal were recorded. RESULTS: A total of 115 HD patients at 6 sites were included in the final analysis. Cumulative catheter use was 10,924 days with a mean duration of 95 days. Seven patients experienced CRBSIs during the study period resulting in a CRBSI rate of 0.64 per 1,000 catheter-days. Seventy-four patients (64.3%) had either elective catheter removal (n = 56) or utilized the catheter for the entire 180-day observation period (n = 18). Thirty-five patients (30%) underwent non-elective device removal either due to CRBSI (n = 5), low flow (n = 16), exit site issues (n = 7), or for other causes (n = 7). Six patients died during the observation period with 1 death due to CRBSI-associated complications and the remaining 5 deaths attributed to non-device related causes. CONCLUSION: Our findings demonstrate that the NexSite HD catheter equipped with ESM technology can achieve a CRBSI rate in compliance with the NKF KDOQI (National Kidney Foundation Kidney Disease Outcome Quality Initiatives) Clinical Performance Guidelines stated goal of less than 1.0/1,000 catheter-days when used in hemodialysis patients using current standard of care nursing protocols.

Effect of a neck collar on upper airway size in children sedated with propofol-midazolam combination during magnetic resonance imaging.

INTRODUCTION: Propofol and midazolam are widely used for pediatric magnetic resonance imaging (MRI) sedation. Increasing depth of sedation may be associated with airway obstruction. A neck collar supporting the mandible and maintaining the head in slight extension may be beneficial in maintaining airway patency. AIM OF THE STUDY: Primary aim: To assess upper airway size with and without a neck collar during pediatric MRI sedation with propofol-midazolam. Secondary aim: To evaluate complications encountered during the procedure. MATERIALS AND METHODS: Sixty patients aged 2-4 years scheduled for MRI of the brain were selected. They were sedated with intramuscular midazolam 0.1 mg·kg(-1) 30 min before the procedure. Patients were sedated with i.v. propofol 1 mg·kg(-1) and continued with 50-100 µg·kg(-1) ·min(-1) . T1 3D fast-field echo axial sequence from the nasopharyngeal roof to subglottic region was taken with and without application of a neck collar. Airway dimensions were measured and analyzed at the base of the tongue, soft palate, and at the epiglottis. RESULTS: At the base of the tongue and soft palate, the cross-sectional area (CSA) and the anteroposterior diameter of the airway were respectively statistically significantly higher when the neck collar was applied. The CSA at the epiglottis was significantly less with application of the neck collar. Complications were not significantly different between the two sequences. CONCLUSION: Application of a soft neck collar in children aged 2-4 years may enhance the retropalatal and retroglossal airway dimensions during pediatric sedation in the supine position.

Nebulized lidocaine alone or combined with fentanyl as a premedication to general anesthesia in spontaneously breathing pediatric patients undergoing rigid bronchoscopy.

INTRODUCTION: Pediatric bronchoscopy is an intensely stimulating procedure that requires a deep level of anesthesia to prevent hemodynamic overstimulation and straining. Topical anesthesia of the airway may be a beneficial component of the anesthetic technique to achieve adequate depth without residual sedation. Experimental evidence suggests that in addition to its central effects, locally applied opioids elicit potent analgesic effects. METHODS: Forty-five patients aged 1-6 years scheduled for rigid bronchoscopy for foreign body removal were selected and subjected preoperatively to a nebulizer setting according to its components patients were divided into three groups. Group A: Nebulized solution contains 4 mg·kg(-1) lidocaine 1%. Group B: Nebulized solution contains 4 mg·kg(-1) lidocaine 1% plus 2 µg·kg(-1) fentanyl. Group C: Nebulized solution contains 0.9% normal saline. Anesthesia was induced with 8% sevoflurane in 100% oxygen and maintained with continuous infusion of propofol 200 µg·kg(-1). Increments of 500 µg·kg(-1) propofol were given to the patient in case of straining or coughing. Patients were followed for the hemodynamics, the intraoperative difficulties, postoperative sedation score, time to full wakefulness and the postoperative complications. RESULTS: The hemodynamic parameters were much more stable in the fentanyl group relative to the other two groups. Also, the incidence of intraoperative difficulties was less significantly evident among patients in the fentanyl group (As regards cough P(1) = 0.003, P(2) = 0.0001, As regards the need to manual ventilation P(1) = 0.037, P(2) = 0.001, As regards Propofol increments P(1) = 0.001, P(2) = 0.001 where P(1) refers to the fentanyl group relative to the lidocaine group, and P(2) refers to fentanyl group relative to the placebo group). The postoperative sedation score was significantly higher, and the time to full wakefulness was significantly prolonged among patients in the fentanyl group relative to the other groups (P = 0.0001). CONCLUSION: It is concluded that preoperative nebulized fentanyl reduces the hemodynamic response to bronchoscopy and decreases the intraoperative coughing in response to surgical manipulation without significant side effects except prolonged time to full wakefulness of patients.

Minimal vs median sternotomy for aortic valve replacement.

The aim of this study was to compare postoperative outcomes in patients undergoing aortic valve replacement through a ministernotomy or conventional sternotomy. Sixty patients were randomized into 2 groups of 30 each: group 1 had a full sternotomy and group 2 had a ministernotomy. Pain was evaluated on a daily basis, pulmonary function tests were performed perioperatively. The skin incision was shorter in group 2 (7.17 vs 24.50 cm in group 1). There was significantly less mediastinal drainage in group 2 (233 vs 590 mL in 24 hours in group 1). Group 1 patients had more blood transfusions and longer ventilation time. In group 1, 96.7% experienced severe pain, whereas 93.3% in group 2 reported minimal pain. Hospital stay was 17.7 days in group 1 and 8.0 days in group 2. The ministernotomy had a cosmetic advantage, less blood loss and transfusion requirement, greater sternal stability, better respiratory function, and earlier extubation and hospital discharge.