Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

An alternative to opioid-based intravenous patient controlled analgesia in severe burn patients undergoing full thickness split graft in upper limbs.

BACKGROUND: Opioids provide good analgesic effect in burn patients during acute phase, but these patients may develop tolerance after prolonged exposure. Alternative analgesic strategies such as peripheral nerve blocks appear to provide adequate pain control while sparing opioid-related side effects. The purpose of this study was to evaluate intravenous patient-controlled analgesia (IV-PCA) and continuous peripheral nerve block (CPNB-PCA) in severe burn patients with relatively young age undergoing repeated debridement and large-area full thickness skin graft (FTSG). METHODS: The records of victims in dust explosion in Taiwan in 2016 from Chang Gung Memorial Hospital Pain Service Database between 2016 June and 2017 December were evaluated. The patients' demographic data including age, gender, weight, burn area, degree of burn, type of PCA regimen (IV-PCA versus CPNB-PCA), size of FTSG, and adverse effects were collected. RESULTS: The total in-hospital morphine consumption was significantly lower in CPNB-PCA than IV-PCA group. A trend of decrease in numerical rating scores (NRS) was observed for both groups and CPNB group had comparable NRS than IV-PCA group at rest. On movement, CPNB grouped had significantly lower NRS than IV-PCA on post-operative day 3. CONCLUSION: Our study demonstrated that in patients requiring high dosage of opioid, CPNB may be a suitable alternative for pain control.

Perioperative transfusion-related acute lung injury: a retrospective analysis.

OBJECTIVE: Transfusion-related acute lung injury (TRALI) is the leading morbidity and mortality in hemotherapy in the United States. Although it is a serious complication of blood transfusion, it is still underestimated and under-reported because of under-recognition and misdiagnosis. In this report, we present 15 surgical patients who developed pulmonary complications secondary to blood transfusion during the perioperative period. METHODS: A 3-year retrospective analysis of 14,441 patients who received blood transfusion intraoperatively in our Taoyuan center was carried out. 15 patients suspected to be subject to TRALI perioperatively were sorted out for analysis of their clinical characteristics. RESULTS: All of the 15 patients received inhalational general anesthesia, of whom 10 were anesthetized with sevoflurane, four with desflurane, and one with isoflurane. One patient died on the first postoperative day due to multiorgan failure whereas 14 others who were managed with oxygen therapy or mechanical ventilation recovered uneventfully within 72 hours. CONCLUSIONS: TRALI must be recognized as one of the leading causes of mortality related to blood transfusion. Oxygen support is often sufficient in mild TRALI while ventilatory support is required in severe TRALI. The strategy to minimize such a risk using blood products from male donors or from female donors without history of pregnancy or having a negative leukocyte antibody screening can help reduce severe immune mediated TRALI.

Spontaneous remission of left bundle branch block immediately after denitrogenation with inhalation of 100% oxygen prior to anesthetic induction.

Complete left bundle branch blocks have focused our attention, primarily because they are a sign predictive of mortality and a predictor of coexisting cardiovascular disease. Left bundle branch block (LBBB) is usually permanent but may occur transiently or intermittently. Spontaneous remission of LBBB rarely occurs during anesthesia. We present two patients in whom chronic LBBB reverted to normal sinus rhythm shortly following denitrogenation with inhalation of 100% oxygen during induction of anesthesia.

Ultrasonic cardiac output monitor provides accurate measurement of cardiac output in recipients after liver transplantation.

BACKGROUND: The ultrasonic cardiac output monitor (USCOM; USCOM Pty. Ltd., Sydney, NSW, Australia) has been accepted as a noninvasive device for measuring cardiac function in various clinical conditions. The present study aimed at comparing the accuracy of this device with that of the thermodilution technique in recipients in the early postoperative period after liver transplantation. METHODS: Fifteen mechanically ventilated patients were studied on the first postoperative day after liver transplantation. We compared the left-sided and right-sided cardiac output (CO) determined by USCOM with that obtained from the thermodilution technique with a pulmonary artery catheter every 8 hours in the intensive care unit. Each patient received a total of four paired measurements. Bland-Altman analysis was used for bias and precision testing. The CO measured by USCOM and the thermodilution method were considered interchangeable if the limits of agreement lay within +/- 1 L per minute or 20% of the mean CO. RESULTS: Forty-eight paired left-sided CO measurements were obtained from 12 patients. Three patients were excluded due to unacceptable signals. Comparison of these two techniques revealed a bias of 0.13 L per minute and limits of agreement at -0.65 L and 0.92 L per minute. Fifty-six paired right-sided CO measurements were obtained from 14 patients with one patient excluded due to an unobtainable optimal signal. A bias of 0.11 L per minute with limits of agreement at -0.51 L and 0.72 L per minute were found for these two techniques. CONCLUSION: This is the first study to evaluate the accuracy of USCOM in the post-liver transplant setting. This device is accurate in measuring CO in liver transplant recipients postoperatively. Possible risks of arrhythmia, infection and pulmonary artery rupture can be avoided because of its noninvasive nature. USCOM should be considered as an alternative in hemodynamic monitoring after liver transplantation.

Reliability of a new ultrasonic cardiac output monitor in recipients of living donor liver transplantation.

The ultrasonic cardiac output monitor (USCOM) is a new Doppler device for noninvasive hemodynamic monitoring. The aim of this prospective nonrandomized study was to test the feasibility, perioperative reliability, and clinical applicability of using USCOM as an alternative to pulmonary artery catheterization in recipients of living donor liver transplantation. Thirteen patients scheduled to receive living donor liver transplants were initially recruited. Three were subsequently excluded prior to the commencement of surgery because of technical difficulties in obtaining diagnostic-quality images with USCOM. Ten patients proceeded to be studied. Cardiac output measurements by thermodilution and USCOM were compared at 30-minute intervals throughout the procedure and at 10 specific procedural reference points during the surgery when hemodynamic changes were most likely to be observed. The data were analyzed with Lin's concordance coefficient and Bland-Altman analysis. Two hundred ninety paired cardiac output values were obtained from the 10 patients. The concordance between both methods was excellent in 8 patients and satisfactory in 2. Bland-Altman analysis of all data produced a mean bias of - 0.02 L/minute for USCOM, and the 95% limits of agreement were -1.06 to +1.10 L/minute. Further analysis of the 10 reference time points showed minimal bias and high levels of agreement between the methods. We conclude that USCOM provides an accurate and noninvasive method for cardiac output measurement during liver transplantation. It may therefore represent an alternative to pulmonary artery catheter placement with consequent reduction in patient's risk and morbidity associated with catheterization. Liver Transpl 14:1029-1037, 2008. (c) 2008 AASLD.

Protection against large-volume regurgitated fluid aspiration by the ProSeal laryngeal mask airway.

The ProSeal laryngeal mask airway (PLMA) is designed to protect the airway from regurgitated fluid. However, successful channeling of large volumes of regurgitated fluid by PLMA is rarely reported. This case report states that a large volume of regurgitated fluid was successfully channeled by a PLMA. The patient was a healthy 43-year-old male, properly fasted, undergoing transurethral cystolithotomy under general anesthesia with a correctly-placed PLMA. Unexpectedly, a large volume of regurgitated fluid (> 500 mL) spurted out from the PLMA esophageal drainage tube 2 hours after surgery. Careful gastric decompression was performed and airway toilet showed no evidence of aspiration of gastric contents. An endotracheal tube was then placed in lieu of the PLMA for airway maintenance. By the end of surgery, 1300 mL of fluid was drained through the gastric tube. Extubation was smooth and the patient had an uneventful recovery. Further radiological examination revealed the existence of an unrecognized vesicorectal fistula, which allowed the cystoscopic irrigation fluid to escape to the GI tract, resulting in massive gastric regurgitation. The patient underwent fistula repair a week later and was discharged without further difficulty. This is a unique clinical case report to show PLMA can be effective in preventing aspiration when massive passive regurgitation occurs. Strategies in the management of massive regurgitation during PLMA use are discussed.

Application of wire-guided endobronchial blocker for one-lung ventilation in patient with tracheostomy--a case report.

One-lung ventilation (OLV) with a double-lumen endotracheal tube or Univent may be achieved difficulty in morbidly obese, mouth opening-limited or critically ill patients. Now, a new fiberoptically directed wire-guided endobronchial blocker (WEB) can be applied for these conditions. We report the use of a new endobronchial blocker in a pharyngeal cancer patient after pharyngectomy. The original 10# Shiley endotracheal tube was exchanged with reinforced cuffed tracheal tube. Then we use the WEB to achieve OLV. The WEB was guided by a loop, and through the appropriate position of left main bronchus by pediatric fiberoptic bronchoscope. Finally, OLV was accomplished smoothly with combination of a non-kinking endotracheal tube and a WEB.

Elevated vascular resistance after labetalol during resection of a pheochromocytoma (brief report).

PURPOSE: To report a case of pheochromocytoma exhibiting an increase in systemic vascular resistance index (SVRI) and decreased cardiac index (CI) after use of labetalol. CLINICAL FEATURES: A 36-yr-old male underwent adrenectomy for pheochromocytoma. Midazolam 5 mg, fentanyl 100 microg and labetalol 20 mg were administrated intravenously for premedication upon arrival in the operating theatre. After induction of anesthesia with fentanyl, thiopental and atracurium, 30 mg iv labetalol was administered. The blood pressure gradually rose to 178/101 mmHg with mildly increased SVRI (1958 dn-sec(-1).m(2).cm(5)) and stable CI (3.8 L.min(-1).m(2) ). The blood pressure reached 247/150 mmHg after intubation with an increase in SVRI (3458 dn-sec(-1).m(2).cm(5)) and a decrease in CI (3.6 L.min(-1).m(2)). The SVRI increased further to 4986 dn-sec(-1).m(2).cm(5) and CI declined to 2.4 L.min(-1).m(2) after the administration of additional labetalol 20 mg. Sodium nitroprusside was administered and the blood pressure declined immediately to 108/72 mmHg, with a decreased SVRI (2526 dn-sec(-1).m(2).cm(5)) and stable CI (2.3 L.min(-1).m(2)). CONCLUSIONS: The elevated SVRI with low CI was considered to result from increased alpha-adrenergic activity secondary to ss-adrenergic blockade with labetalol. Clinicians should be aware of the possibility of a hypertensive crisis after iv labetalol. We suggest that labetalol should be replaced promptly with alpha-adrenergic blockers or other vasodilators when such a condition arises.