Prophylactic dexamethasone for rebound pain after peripheral nerve block in adult surgical patients: systematic review, meta-analysis, and trial sequential analysis of randomised controlled trials.

BACKGROUND: Rebound pain occurs after the resolution of peripheral nerve block and hampers patient recovery in the postoperative period. We sought to synthesise available data from randomised controlled trials (RCTs) evaluating the efficacy of prophylactic dexamethasone for rebound pain in adult patients undergoing surgery with a peripheral nerve block. METHODS: In this systematic review and meta-analysis, RCTs reporting rebound pain and use of dexamethasone in the context of a peripheral nerve block were searched in various databases and updated in May 2023. The primary outcome was the incidence of rebound pain; secondary outcomes included the severity and time to onset of rebound pain, patient satisfaction with pain control, sleep disturbance because of pain, and adverse effects of dexamethasone. Subgroup analysis was conducted based on the effect of route of administration (intravenous or perineural) on the incidence of rebound pain. Trial sequential analysis was performed to rule out the possibility of a false positive result. RESULTS: Seven RCTs comprising 574 patients were included in this review. The dexamethasone group was associated with a reduction in the incidence of rebound pain with an odds ratio of 0.16 (95% confidence interval 0.10-0.27, P=0.00, I2=0%) compared with the control group. Trial sequential analysis confirmed the adequate information size for the beneficial effect of dexamethasone. Subgroup analysis showed that both intravenous and perineural administration were associated with a significant reduction in the incidence of rebound pain. CONCLUSIONS: Current evidence suggests that both intravenous and perineural dexamethasone reduce the incidence of rebound pain after a peripheral nerve block provided for postoperative analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023424031.

Emergency use of sugammadex after failure of standard reversal drugs and postoperative pulmonary complications: A retrospective cohort study.

Background and Aims: The use of sugammadex instead of neostigmine for the reversal of neuromuscular blockade may decrease postoperative pulmonary complications. It is unclear if this finding is applicable to situations where sugammadex is administered after the administration of neostigmine. The objective of this study was to compare the incidence of a composite outcome measure of major postoperative pulmonary complications in patients who received sugammadex as a rescue agent after neostigmine versus those who received sugammadex alone for reversal of neuromuscular blockade. Material and Methods: This retrospective cohort study analyzed the medical records of adult patients who underwent elective inpatient noncardiac surgery under general anesthesia and received sugammadex for reversal of neuromuscular blockade, at a tertiary care academic hospital between August 2016 and November 2018. Results: A total of 1,672 patients were included, of whom 1,452 underwent reversal with sugammadex alone and 220 received sugammadex following reversal with neostigmine/glycopyrrolate. The composite primary outcome was diagnosed in 60 (3.6%) patients. Comparing these two groups, and after adjusting for confounding factors, patients who received sugammadex after reversal with neostigmine had more postoperative pulmonary complications than those reversed with sugammadex alone (6.8% vs. 3.1%, odds ratio, 2.29; 95% confidence interval [CI], 1.25 to 4.18; P = 0.006). Conclusion: The use of sugammadex following reversal with neostigmine was associated with a higher incidence of postoperative pulmonary complications as compared to the use of sugammadex alone. The implications of using sugammadex after the failure of standard reversal drugs should be investigated in prospective studies.

Determination of the optimal length of insertion for central venous catheterization via axillary vein cannulation using preoperative chest X-ray- A prospective feasibility study.

Background and Aims: Ensuring safe central venous catheter tip placement is important. Multiple techniques are available to estimate the length of catheter insertion for subclavian and internal jugular approaches. However, the methods to determine the length of insertion for the axillary route have not been validated. The purpose of this feasibility study was to evaluate a simple method for the calculation of catheter length to be inserted and assess whether it accurately predicts the correct tip placement. Material and Methods: A total of 102 patients requiring preoperative central venous cannulation were evaluated, out of which 60 had successful axillary vein (AxV) cannulation. The length of insertion was calculated using the formula: (2/3* A + B) +Y (A: Clavicular length on chest radiograph [CXR], B: Vertical distance between the sternal head and carina on CXR, Y: Perpendicular distance from the skin to the AxV on ultrasound). A postoperative CXR was used to assess the accurate tip placement (2 cm above the carina to 0.5 cm below it). The primary outcome of the study was the rate of successful placement of the central venous catheter (CVC) in terms of the correct position of the tip of the catheter when the length of the catheter inserted was predicted by the formula described previously. Results: Optimal placement was observed in 83.33% of the cases. A higher rate of accuracy was seen in the females (P value = 0.03) and shorter patients (P value = 0.01). A Bland-Altman plot depicted a high degree of agreement. Conclusion: Use of the formula using a CXR and ultrasound allowed P successful placement of the CVC tip at the desired location in 83.33% of the cases.

Pharmacological agents for prevention of pruritus in women undergoing Caesarean delivery with neuraxial morphine: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Neuraxial opioids provide effective analgesia for Caesarean delivery, however, pruritus can be a troubling side-effect. Effective agents to prevent pruritus are needed. Our objective was to perform an updated systematic review and network meta-analysis to provide clinicians with a comparison of relative efficacy of available interventions to reduce the incidence of pruritus, induced by either intrathecal or epidural single-shot morphine, in women undergoing Caesarean delivery. METHODS: Databases systematically searched (up to January 2022) included PubMed MEDLINE, Web of Science, EBSCO CINAHL, Embase, LILACS, and two Cochrane databases. We included randomised, controlled trials involving adult female patients undergoing Caesarean delivery. We pooled trials comparing interventions used for preventing pruritus after Caesarean delivery and performed a Bayesian model network meta-analysis. RESULTS: The final primary network included data from comparisons of 14 distinct interventions (including placebo) used to reduce the incidence of pruritus in 6185 participants. We judged five interventions to be 'definitely superior' to placebo: propofol, opioid agonist-antagonists (neuraxial), opioid antagonists, opioid agonist-antagonists (systemic), and serotonin antagonists. For the network evaluating the incidence of severe pruritus (warranting additional therapeutic treatment of pruritus), data were available for 14 interventions (including placebo) in 4489 patients. For this outcome, we judged three interventions to be 'definitely superior' to placebo: dopamine antagonists (neuraxial) and systemic and neuraxial opioid agonist-antagonists. CONCLUSION: Our analysis found several interventions to be effective in reducing the incidence of pruritus. Although sub-hypnotic doses of propofol appear to have an antipruritic effect, replication of this finding and further investigation of optimal dosing are warranted. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022367058).

Analgaesic efficacy of single-injection serratus anterior plane block for breast surgery: A systematic review, meta-analysis and trial sequential analysis of randomised controlled trials.

There is conflicting evidence regarding the analgaesic efficacy of single-shot serratus anterior plane block (SAP) for breast surgery. This meta-analysis aimed to evaluate the analgaesic efficacy of SAP compared with non-block care (NBC) and other regional blocks, i.e. paravertebral block (PVB) and modified pectoral nerve block (PECS block) for breast surgery. PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched. We included randomized controlled trials reporting the use of the SAP block in adult breast surgery. The primary outcome was postoperative oral morphine equivalent (OME) consumption for up to 24 hours. Random-effects models were used to pool results and mean difference (MD), and odds ratio (OR) was calculated for continuous and dichotomous outcomes, respectively. GRADE guidelines were used to evaluate the strength of evidence, and trial sequential analysis (TSA) was performed to provide certainty to the conclusion. Twenty-four trials enrolling 1789 patients were included. Moderate strength evidence suggested that SAP provided a significant reduction in 24-hour OME compared with NBC [MD - 24.9 mg (95% CI - 41.54, -8.25; P < 0.001, I2 = 99.68%)]. TSA ruled out the possibility of false-positive results. Subgroup analysis for the SAP demonstrated that the superficial plane approach was more effective in reducing opioid consumption than the deep approach. The odds of developing PONV were significantly lower in SAP compared to NBC. Compared with PVB and PECS, SAP block was not statistically different for 24-hour OME and time to first rescue analgaesia. Single-shot SAP reduced opioid consumption, prolonged analgaesia duration, lowered pain scores, and decreased the incidence of PONV compared to NBC. There was no statistically significant difference in the studied endpoints between SAP, PVB, and PECS blocks.

Effect of Change in Body Weight on Clinical Outcomes in Critically Ill Patients.

BACKGROUND: Intravenous fluid optimization is an essential component of managing patients in a critical care setting. A cumulative positive fluid balance is consistent with poor outcomes in patients admitted to the intensive care unit (ICU). The overall utility of net cumulative fluid balance as a surrogate for assessing fluid overload has been interrogated. MATERIALS AND METHODS: This study was a prospective single-center observational study, which was done to correlate body weight changes with fluid balance in ICU patients and evaluate its impact on clinical outcomes. Inclusion criteria consisted of adult patients who were admitted to the critical care unit on specialized beds with integrated weighing scales between September 2017 and December 2018. The evaluation of the effect of changes in body weight on ICU survival was the primary objective of the study. RESULTS: We enrolled 105 patients in this study. The ICU mortality was 23.80% with non-survivors showing more weight gain than the survivors. Statistically significant weight gain was documented in the non-survivors on days 3 and 4 (1.9 vs 1.05; p = 0.0084 and 2.6 vs 1.6; p = 0.0030) of ICU admission. Non-survivors had greater cumulative positive fluid balance on fourth, fifth, and sixth days post-ICU admission when compared to survivors (3586 vs 1659 mL, p = 0.0322; 5418 vs 1255 mL, p = 0.0017; and 5430 vs 2305 mL p = 0.0264, respectively). In multivariate regression analysis, cumulative fluid balance did not correlate with days on mechanical ventilation or length of stay in ICU. Changes in body weight and cumulative fluid balance showed a good correlation. CONCLUSION: In patients admitted to the ICU, weight gain on third and fourth days of admission is concordant with increased ICU mortality. Body weight changes were seen to correlate well with the cumulative fluid balance. HOW TO CITE THIS ARTICLE: Mishra RK, Pande A, Ramachandran R, Trikha A, Singh PM, Rewari V. Effect of Change in Body Weight on Clinical Outcomes in Critically Ill Patients. Indian J Crit Care Med 2021;25(9):1042-1048.

Scientometric analysis of medical publications during COVID-19 pandemic: the twenty-twenty research boom.

INTRODUCTION: There was significant surge in the academic publications after the onset of COVID-19 outbreak. The aim of this study was to scientometrically analyze all the medical publications on COVID-19 in 2020 as well as the top 100 cited articles. EVIDENCE ACQUISITION: We performed a search of the "Web of Science" database using the keywords "COVID," and "corona" on December 20, 2020. EVIDENCE SYNTHESIS: Our search retrieved a total of 45,420 articles on the topic COVID-19 in the year 2020. Corresponding authors from 143 countries contributed to these articles. The highest number of articles were contributed by corresponding authors from the USA (N.=10299), whereas 50 articles in the top 100 cited articles had corresponding authors from China. Among the top 100 cited, the majority were published from Huazhong University of Science and Technology in China (N.=37). New England Journal of Medicine had the maximum impact (h-index of 57), closely followed by Lancet (h-index=55). CONCLUSIONS: Scientific publications amount on COVID-19 disease grew at an astonishing pace during 2020. We caution the readers that this rapidity of publication could have missed out on the rigorous review process and the scientific basis of the methods followed.

Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial.

Persistent tachycardia in patients with septic shock predicts poor outcome. This study sought to investigate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and cardio-circulatory function in patients with septic shock. After informed consent, 60 patients with septic shock and persistent tachycardia (heart rate >95 /minute) were prospectively randomly assigned to receive either standard therapy for septic shock (group S) or standard therapy along with enteral ivabradine (group I) for the initial 96 hours after enrolment. Primary outcome was the difference in heart rate between the two groups during the first 96 hours. Secondary outcomes included the effect of ivabradine on haemodynamic, oxygenation, myocardial function and organ function parameters, incidence of adverse events and 30-day overall survival. Heart rate was lower in group I compared to group S (median difference in area under the curve -25.6 (95% confidence intervals -31.4 to -15.9) /minute; P <0.001). Vasopressor requirements, blood lactate levels, Sequential Organ Failure Assessment scores and E/e' ratio were lower in group I compared to group S. Stroke volume index and ejection fraction were higher in group I while cardiac index and oxygen delivery parameters were maintained similar to group S. There was no difference in 30-day mortality or in the incidence of serious adverse events. Enteral ivabradine is effective in reducing heart rate, and improving haemodynamic parameters and cardiac function in patients with septic shock and persistent tachycardia, without increasing the incidence of adverse events.

A systematic review of patient-reported outcome measures to assess postpartum pain using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.

BACKGROUND: We performed a systematic review using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines to identify the best available patient-reported outcome measure (PROM) of postpartum pain. METHODS: This review follows COSMIN guidelines. We searched four databases with no date limiters, for previously identified validated PROMs used to assess postpartum pain. PROMs evaluating more than one author-defined domain of postpartum pain were assessed. We sought studies evaluating psychometric properties. An overall rating was then assigned based upon COSMIN analysis, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the level of evidence for psychometric properties of included PROMs. These assessments were used to make recommendations and identify the best PROM to assess postpartum pain. RESULTS: We identified 19 studies using seven PROMs (involving 3511 women), which evaluated postpartum pain. All included studies evaluated ≥1 psychometric property of the included PROMs. An adequate number of pain domains was assessed by the Brief Pain Inventory (BPI), Short Form-BPI (SF-BPI), and McGill Pain Questionnaire (MPQ). The SF-BPI was the only PROM to demonstrate adequate content validity and at least a low-level of evidence for sufficient internal consistency, resulting in a Class A recommendation (the best performing instrument, recommended for use). CONCLUSION: SF-BPI is the best currently available PROM to assess postpartum pain. However, it fails to assess several important domains and only just met the criteria for a Class A recommendation. Future studies are warranted to develop, evaluate, and implement a new PROM designed to specifically assess postpartum pain.

Temporal Evolution of the PcvCO2-PaCO2/CaO2-CcvO2 Ratio vs Serum Lactate during Resuscitation in Septic Shock.

BACKGROUND: Lactate as a target for resuscitation in patients with septic shock has important limitations. The PcvCO2-PaCO2/CaO2-CcvO2 ratio may be used as an alternative for the same. The primary outcome of the study is to evaluate the correlation between serum lactate and PcvCO2-PaCO2/CaO2-CcvO2 ratio measured at various time points to a maximum of 24 hours in patients with septic shock [mean arterial pressure (MAP) <65 mm Hg]. The secondary outcomes were to study the (1) relationship between the PcvCO2-PaCO2/CaO2-CcvO2 ratio and lactate clearance at 6, 12, and 24 hours as compared to the initial serum lactate, (2) to ascertain whether the PcvCO2-PaCO2/CaO2-CcvO2 ratio and the arterial lactate levels in the first 24 hours are able to predict mortality at day 28 of enrollment, and (3) to determine whether the PcvCO2-PaCO2/ CaO2-CcvO2 ratio and arterial lactate are useful in discriminating survivors from nonsurvivors. MATERIALS AND METHODS: Thirty patients with sepsis-induced hypotension who were being actively resuscitated were enrolled. Paired arterial and central venous blood samples were obtained 0.5 hourly till stabilization of MAP and 6 hourly thereafter for the first 24 hours. Patients were followed up to day 28 of enrollment for mortality and organ system failure. RESULTS: A positive correlation was observed between arterial lactate and PcvCO2-PaCO2/CaO2-CcvO2 ratio at 0, 6, 12, and 18 hours (R = 0.413, p = 0.02; R = 0.567, p = 0.001; R = 0.408, p = 0.025; R = 0.521, p = 0.003, respectively). No correlation was seen between PcvCO2-PaCO2/CaO2-CcvO2 ratio and lactate clearance. The subgroup analysis showed that PcvCO2-PaCO2/CaO2-CcvO2 ratio >1.696 at 24 hours of resuscitation predicted 28-day mortality (sensitivity: 80%, specificity 69.2%, area under the receiver operating characteristic curve 0.82). CONCLUSION: The PcvCO2-PaCO2/CaO2-CcvO2 ratio and lactate are positively correlated during the first 24 hours of active resuscitation from sepsis-induced hypotension, and a threshold of 1.696 mm Hg/mL/dL at 24 hours significantly differentiates survivors from nonsurvivors (CTRI/2017/11/010342). HOW TO CITE THIS ARTICLE: Madabhushi S, Trikha A, Anand RK, Ramachandran R, Singh PM, Rewari V. Temporal Evolution of the PcvCO2-PaCO2/CaO2-CcvO2 Ratio vs Serum Lactate during Resuscitation in Septic Shock. Indian J Crit Care Med 2021; 25(12):1370-1376.

Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for Caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes.

BACKGROUND: The optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes. METHODS: RCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and Pco2. Maternal outcomes were incidences of nausea, vomiting, and bradycardia. RESULTS: We included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and Pco2. With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks. CONCLUSION: Our analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine.

Role of Decompressive Craniectomy in Traumatic Brain Injury - A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Several studies have indicated that decompressive craniectomy (DC) for traumatic brain injury (TBI) is lifesaving. However, there is lack of level 1 evidence to define the role of DC in TBI. We performed a meta-analysis of all the randomized controlled trials (RCTs) published so far on the role of DC in adult patients with TBI. MATERIALS AND METHODS: A systematic literature search was performed for articles published until September of 2016 for RCTs of DC in adult patients with TBI. The primary end-point was mortality at six-months. We also evaluated the overall adverse outcomes at six months. Assessment of risk of bias of the RCTs was also performed. RESULTS: Three trials evaluating adult population satisfied the eligibility criteria. Pooled analysis involved 285 and 288 patients in DC group and control groups respectively. Patients undergoing DC for TBI had a lower mortality association of nearly 50 percent. However, patients surviving DC were more likely to have a poor neurological outcome compared to patients undergoing medical management. CONCLUSION: Based on the available RCTs on DC in TBI, the results of our meta-analysis show that there is a mortality benefit of performing a DC over the best medical management in adult patients. Furthermore, surviving following DC, a greater incidence of a poor neurological outcome is noted. In the event of small number of high-quality RCTs, our results must be interpreted with caution.

Pre-emptive multimodal analgesic regimen reduces post-operative epidural demand boluses in traumatic shaft of femur fracture - A randomised controlled trial.

BACKGROUND AND AIMS: The efficacy of preemptive multimodal analgesia in post-traumatic patients has not been elucidated. Our aim was to evaluate the efficacy of preemptive MMA regimen in reducing the epidural demand boluses in the first 48 hours following the traumatic shaft of femur fractures. METHODS: Patients scheduled for traumatic femur fracture surgery were randomised (n = 135) into two groups in this double blind, placebo controlled trial. Patients received either (Preemptive multimodal group) intravenous acetaminophen 1 gm, diclofenac 75 mg, morphine 3 mg, 75 mg Pregabalin (per oral) or a placebo 30 minutes pre-operatively. Intra-operatively, all patients were managed with spinal and epidural anaesthesia. Post-operatively, patients received patient-controlled epidural analgesia (PCEA) programmed to deliver a bolus of 5 ml of 0.2% Ropivacaine with 2 µg/ml of Fentanyl with lockout interval time of 15 min. Primary outcome was number of PCEA boluses received post-operatively over 48 h. Secondary outcomes measures were time to receive first epidural bolus, postoperative VAS scores and episodes of post-operative nausea, vomiting and sedation. Total number of PCEA bolus doses over 48 hours and VAS scores were analysed using Mann-Whitney test. RESULTS: Significant reduction in median number of demand boluses were observed in preemptive multimodal group (3 [2-4]) compared to placebo group (5 [4-7]); P = 0.00. Time to first rescue epidural bolus was significantly greater in preemptive multimodal group than placebo group. CONCLUSION: The use of preemptive MMA regimen reduced the requirement of demand epidural bolus doses.

Role of topical magnesium in post-operative sore throat: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND AND AIMS: Post-operative sore throat (POST) is a common undesirable consequence of tracheal intubation. Magnesium, an N-methyl-D-aspartate receptor antagonist, has anti-nociceptive and anti-inflammatory properties, and has been found to be useful in POST prevention in various trials. We conducted this systematic review and meta-analysis to study the efficacy of topical magnesium in preventing POST in adult patients undergoing surgery under general anaesthesia with single lumen tracheal tube. METHODS: Comprehensive literature search was performed in PubMed, Google Scholar, EMBASE, Scopus and the Cochrane central registers of controlled trial databases through July, 2018 and data were pooled using fixed effect modelling followed by random-effect methods (after assessing heterogeneity with fixed modelling). The primary outcome was the incidence of POST at 24 h after surgery/extubation. Comparative results were deliberated as pooled mean difference for continuous variables and Mantel-Haenszel (MH) odds ratio for dichotomous variables. Statistical analysis was done using Comprehensive Meta-Analysis-Version 3 (Biostat Inc., USA). RESULTS: Seven trials involving 726 study participants were included in the final analysis. Incidence of POST at 24 hours was significantly lower in magnesium group (26/363) in comparison to active and non-active control group (89/363); P = 0.00- RR 0.22 (95%CI = 0.12-0.39, I2 = 0%). No significant adverse events were reported with the use of topical magnesium. CONCLUSION: Prophylactic use of topical magnesium before the induction of general anaesthesia seems to be an effective measure to decrease the incidence of POST.

Development of ALD Coatings for Harsh Environment Applications.

Atomic layer deposition (ALD) is a well-known technique for the fabrication of ultrathin and highly conformal barrier coatings which have extensively been used for the protection of electronic devices in open atmospheric conditions. Here, we extend the scope for the application of low-temperature-deposited plasma-enhanced ALD barrier coatings for the protection of devices in a variety of chemical environments. The chemical stability tests were conducted in 3.5% NaCl, sea water, HCl (pH 4), and H2SO4 (pH 4) solutions for ALD Al2O3, HfO2, TiO2, and ZrO2, deposited at 100 °C on TiO2-coated Au and ALD ZnO (photoactive)-coated Si substrates. Using electrochemical impedance spectroscopy (EIS) and photoluminescence (PL) study, various aspects of the barrier properties and performance of ALD films in harsh chemical environments were explored. We demonstrate that the combined approach involving EIS and PL provides unique insights into the suitability of ALD films as barriers in harsh environments involving ionic solutions. The observations from EIS and PL tests are supported by the X-ray photoelectron spectroscopy analysis of ALD materials. Of the materials tested, ALD TiO2 and ZrO2 were found to be the most stable, chemically, in all four solutions, whereas TiO2 was a better permeation barrier.

Inhibition of Bacterial Adhesion on Nanotextured Stainless Steel 316L by Electrochemical Etching.

Bacterial adhesion to stainless steel 316L (SS316L), which is an alloy typically used in many medical devices and food processing equipment, can cause serious infections along with substantial healthcare costs. This work demonstrates that nanotextured SS316L surfaces produced by electrochemical etching effectively inhibit bacterial adhesion of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, but exhibit cytocompatibility and no toxicity toward mammalian cells in vitro. Additionally, the electrochemical surface modification on SS316L results in formation of superior passive layer at the surface, improving corrosion resistance. The nanotextured SS316L offers significant potential for medical applications based on the surface structure-induced reduction of bacterial adhesion without use of antibiotic or chemical modifications while providing cytocompatibility and corrosion resistance in physiological conditions.

Sustained-Release Injectable Hydrogel Formulations for Administration of Sodium Salicylate in Broiler Chickens.

We developed injectable hydrogels for the slow release of analgesic drugs in birds as an in vivo model of pharmacokinetics in wild avian species. Hydrogels loaded with sodium salicylate (NaSA) were injected subcutaneously in Ross broiler chickens. The hydrogels were made by dissolving sodium alginate and NaSA in water at 2 different concentrations (low, LALG; high, HALG) and then adding calcium chloride. In vitro drug release studies were performed by swelling the hydrogels in water and analyzing serial samples by ultraviolet-visible (UV-Vis) spectroscopy. Dried hydrogel films of the same formulations of the two alginate concentrations then were dissolved in sterile water for the in vivo pharmacokinetic study conducted in 18 chickens divided into 3 groups of 6 birds. Each of the 2 resultant NaSA hydrogel solutions were filtered with 0.2-µm syringe filters before injecting at a NaSA dose of 150 mg/kg SC in the respective LALG or HALG groups. The control group was injected SC with the same dose of NaSA dissolved in water. Pharmacokinetics parameters calculated by the compartmental and noncompartmental approaches were compared among the 3 groups by the Kruskal-Wallis test. Results of in vitro studies showed that both hydrogels released 80% of the drug during the first 3.5 hours. Results of the pharmacokinetic study indicated that NaSA concentrations remained above the minimum effective concentration (MEC) for analgesia in humans for 24 ± 8.9 (LALG) to 26 ± 4 (HALG) hours for the hydrogel formulations compared to 10 ± 5.6 hours for the aqueous formulation. These hydrogel formulations may have potential in providing long-term analgesia in avian species, but need further evaluation with pharmacodynamic or pharmacokinetic/pharmacodynamic modeling studies.

Effect of choline chloride premedication on xylazine-induced hypoxaemia in sheep.

OBJECTIVE: To determine the anti-inflammatory efficacy of choline in vivo and in vitro and to investigate the anti-inflammatory mechanisms of choline. STUDY DESIGN: Randomized, controlled studies. ANIMALS: In vivo trials used 16 Romney sheep. In vitro experiments utilized RAW 264.7 mouse macrophage cells. METHODS: Hypoxaemia induced in 16 sheep by intravenous (IV) injection of 50 µg kg-1 xylazine, an α-2 agonist, was measured in sheep at 0, 1 and 4 minutes using arterial blood gas analysis with and without 50 mg kg-1 IV choline chloride premedication. Cell culture studies used enzyme-linked immunosorbent assay to measure the release of tumour necrosis factor (TNF-α) from lipopolysaccharide (LPS) stimulated macrophages with and without choline chloride premedication. TNF-α release was compared to thalidomide suppressed and untreated cells. RESULTS: Choline premedication in sheep mitigated a reduction in arterial partial pressure of oxygen (PaO2) but did not prevent development of clinically significant hypoxaemia. Decrease in mean PaO2 of choline treated sheep was 6.36 kPa (47.7 mmHg) compared to 9.81 kPa (73.6 mmHg) in control sheep. In vitro studies demonstrate that choline administered concurrent with LPS activation did not significantly suppress TNF-α expression but that treatment of cells with choline 10 minutes prior to LPS activation did significantly suppress TNF-α expression. Choline pretreated cells expressed 23.99 ± 4.52 ng mg-1 TNF-α while LPS only control cells expressed 33.83 ± 3.20 ng mg-1. CONCLUSIONS: Choline is able to prevent macrophage activation in vitro when administered prior to LPS activation and may reduce hypoxaemia in sheep developing pulmonary oedema after xylazine administration. This effect requires premedication with choline. CLINICAL RELEVANCE: Pharmacological manipulation of autonomic inflammatory responses holds promise for the treatment of inflammation. However, the complex cellular mechanisms involved in this reflex means that an adequate therapy should approach multiple pathways and mechanisms of the inflammatory response.