Ventilación no invasiva con presión positiva (CPAP o doble nivel) para el edema agudo de pulmón cardiogénico / Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema

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The serratus plane block for postoperative analgesia in breast and thoracic surgery: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The serratus plane block (SPB) is a novel chest wall interfascial plane block. Its analgesic efficacy compared with non-block care and paravertebral block (PVB) is unestablished. METHODS: We conducted a random-effects meta-analysis of randomized controlled trials (RCTs) recruiting adult surgical patients that compared a SPB to non-block care or PVB for postoperative analgesia. Visual analog scale pain scores were the primary outcome. Database sources were Medline, Embase, the Cochrane Library, and Google Scholar searched up to July 29, 2019 without language restriction. Risk of bias was assessed using Cochrane methodology. RESULTS: Nineteen RCTs that comprised 1260 patients were included. Six trials involved thoracic surgery patients and 13 studied breast surgery patients. SPB reduced pain scores 0 hour postoperatively (-1.62 cm; 99% CI -2.43 to -0.81; p<0.001; I2=92%), at 2-4 hours (-1.29 cm; 99% CI -2.08 to -0.49; p<0.001; I2=92%), at 6 hours (-1.69 cm; 99% CI -3.19 to -0.20; p=0.004; I2=99%), and up to 24 hours compared with non-block care. SPB also prolonged the time to first analgesic request (193.2 min; 95% CI 7.2 to 379.2 min; p=0.04; I2=99%), reduced 24-hour postoperative opioid consumption (-11.27 mg of IV morphine equivalent; -17.36 to -5.18 mg; p<0.001), and reduced postoperative nausea and vomiting (RR 0.51; 95% CI 0.38 to 0.68; p<0.001; I2=12%). In contrast, no meaningful differences were detected in any of the outcomes for the SPB versus PVB data. CONCLUSIONS: SPB reduced postoperative pain scores (Grading of Recommendations Assessment, Development, and Evaluation rating: low; due to heterogeneity and deficiencies in blinding) in breast and thoracic surgery patients compared with non-block care. Based on five trials only, SPB was not appreciably different from PVB.

Challenges With Continuous Pulse Oximetry Monitoring and Wireless Clinician Notification Systems After Surgery: Reactive Analysis of a Randomized Controlled Trial.

BACKGROUND: Research has shown that introducing electronic Health (eHealth) patient monitoring interventions can improve healthcare efficiency and clinical outcomes. The VIGILANCE (VItal siGns monItoring with continuous puLse oximetry And wireless cliNiCian notification aftEr surgery) study was a randomized controlled trial (n=2049) designed to assess the impact of continuous vital sign monitoring with alerts sent to nursing staff when respiratory resuscitations with naloxone, code blues, and intensive care unit transfers occurred in a cohort of postsurgical patients in a ward setting. This report identifies and evaluates key issues and challenges associated with introducing wireless monitoring systems into complex hospital infrastructure during the VIGILANCE eHealth intervention implementation. Potential solutions and suggestions for future implementation research are presented. OBJECTIVE: The goals of this study were to: (1) identify issues related to the deployment of the eHealth intervention system of the VIGILANCE study; and (2) evaluate the influence of these issues on intervention adoption. METHODS: During the VIGILANCE study, issues affecting the implementation of the eHealth intervention were documented on case report forms, alarm event forms, and a nursing user feedback questionnaire. These data were collated by the research and nursing personnel and submitted to the research coordinator. In this evaluation report, the clinical adoption framework was used as a guide to organize the identified issues and evaluate their impact. RESULTS: Using the clinical adoption framework, we identified issues within the framework dimensions of people, organization, and implementation at the meso level, as well as standards and funding issues at the macro level. Key issues included: nursing workflow changes with blank alarm forms (24/1030, 2.33%) and missing alarm forms (236/1030, 22.91%), patient withdrawal (110/1030, 10.68%), wireless network connectivity, false alarms (318/1030, 30.87%), monitor malfunction (36/1030, 3.49%), probe issues (16/1030, 1.55%), and wireless network standards. At the micro level, these issues affected the quality of the service in terms of support provided, the quality of the information yielded by the monitors, and the functionality, reliability, and performance of the monitoring system. As a result, these issues impacted access through the decreased ability of nurses to make complete use of the monitors, impacted care quality of the trial intervention through decreased effectiveness, and impacted productivity through interference in the coordination of care, thus decreasing clinical adoption of the monitoring system. CONCLUSIONS: Patient monitoring with eHealth technology in surgical wards has the potential to improve patient outcomes. However, proper planning that includes engagement of front-line nurses, installation of appropriate wireless network infrastructure, and use of comfortable cableless devices is required to maximize the potential of eHealth monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT02907255; https://clinicaltrials.gov/ct2/show/NCT02907255.

Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been used to treat respiratory distress due to acute cardiogenic pulmonary oedema (ACPE). We performed a systematic review and meta-analysis update on NPPV for adults presenting with ACPE. OBJECTIVES: To evaluate the safety and effectiveness of NPPV compared to standard medical care (SMC) for adults with ACPE. The primary outcome was hospital mortality. Important secondary outcomes were endotracheal intubation, treatment intolerance, hospital and intensive care unit length of stay, rates of acute myocardial infarction, and adverse event rates. SEARCH METHODS: We searched CENTRAL (CRS Web, 20 September 2018), MEDLINE (Ovid, 1946 to 19 September 2018), Embase (Ovid, 1974 to 19 September 2018), CINAHL Plus (EBSCO, 1937 to 19 September 2018), LILACS, WHO ICTRP, and clinicaltrials.gov. We also reviewed reference lists of included studies. We applied no language restrictions. SELECTION CRITERIA: We included blinded or unblinded randomised controlled trials in adults with ACPE. Participants had to be randomised to NPPV (continuous positive airway pressure (CPAP) or bilevel NPPV) plus standard medical care (SMC) compared with SMC alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected articles for inclusion. We extracted data with a standardised data collection form. We evaluated the risks of bias of each study using the Cochrane 'Risk of bias' tool. We assessed evidence quality for each outcome using the GRADE recommendations. MAIN RESULTS: We included 24 studies (2664 participants) of adult participants (older than 18 years of age) with respiratory distress due to ACPE, not requiring immediate mechanical ventilation. People with ACPE presented either to an Emergency Department or were inpatients. ACPE treatment was provided in an intensive care or Emergency Department setting. There was a median follow-up of 13 days for hospital mortality, one day for endotracheal intubation, and three days for acute myocardial infarction. Compared with SMC, NPPV may reduce hospital mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.82; participants = 2484; studies = 21; I2 = 6%; low quality of evidence) with a number needed to treat for an additional beneficial outcome (NNTB) of 17 (NNTB 12 to 32). NPPV probably reduces endotracheal intubation rates (RR 0.49, 95% CI 0.38 to 0.62; participants = 2449; studies = 20; I2 = 0%; moderate quality of evidence) with a NNTB of 13 (NNTB 11 to 18). There is probably little or no difference in acute myocardial infarction (AMI) incidence with NPPV compared to SMC for ACPE (RR 1.03, 95% CI 0.91 to 1.16; participants = 1313; studies = 5; I2 = 0%; moderate quality of evidence). We are uncertain as to whether NPPV increases hospital length of stay (mean difference (MD) -0.31 days, 95% CI -1.23 to 0.61; participants = 1714; studies = 11; I2 = 55%; very low quality of evidence). Adverse events were generally similar between NPPV and SMC groups, but evidence was of low quality. AUTHORS' CONCLUSIONS: Our review provides support for continued clinical application of NPPV for ACPE, to improve outcomes such as hospital mortality and intubation rates. NPPV is a safe intervention with similar adverse event rates to SMC alone. Additional research is needed to determine if specific subgroups of people with ACPE have greater benefit of NPPV compared to SMC. Future research should explore the benefit of NPPV for ACPE patients with hypercapnia.

Vital sign monitoring with continuous pulse oximetry and wireless clinical notification after surgery (the VIGILANCE pilot study)-a randomized controlled pilot trial.

BACKGROUND: Respiratory depression is a serious perioperative complication associated with morbidity and mortality. Recently, technology has become available to wirelessly monitor patients on regular surgical wards with continuous pulse oximetry and wireless clinician notification with alarms. When a patient's SpO2 falls below a set threshold, the clinician is notified via a pager and may intervene earlier to prevent further clinical deterioration. To date, the technology has not been evaluated with a randomized controlled trial (RCT). METHODS: We designed a parallel-group unblinded pilot RCT of a wireless monitoring system on two surgical wards in an academic teaching hospital. Postsurgical patients with an anticipated length of stay of at least 1 day were included and randomized to standard care or standard care plus wireless respiratory monitoring for up to a 72-h period. The primary outcomes were feasibility outcomes: average patients recruited per week and tolerability of the system by patients. Secondary outcomes included (1) respiratory events (naloxone administration for respiratory depression, ICU transfers, and cardiac arrest team activation) and (2) system alarm types and details. The analysis of the outcomes was based on descriptive statistics and estimates reported using point (95% confidence intervals). Criteria for success of feasibility were recruitment of an average of 15 patients/week and 90% of the patients tolerating the system. RESULTS: The pilot trial enrolled 250 of the 335 patients screened for eligibility, with 126 and 124 patients entering the standard monitoring and wireless groups, respectively. Baseline demographics were similar between groups, except for slightly more women in the wireless group. Average patient recruitment per week was 14 95% CI [12, 16] patients. The wireless monitoring was quite tolerable with 86.6% (95% CI 78.2-92.7%) of patients completing the full course, and there were no other adverse events directly attributable to the monitoring. With regard to secondary outcomes, the respiratory event rate was low with only 1 event in the wireless group and none in the control group. The average number of alarms per week was 4.0 (95% CI, 1.6-6.4). CONCLUSIONS: This pilot study demonstrated adequate patient recruitment and high tolerability of the wireless monitoring system. A full RCT that is powered to detect patient important outcomes such as respiratory depression is now underway. TRIAL REGISTRATION: ClinicalTrials.gov, Registration number NCT02907255, registered 7 September 2016-retrospectively registered.

Dexamethasone as an Adjuvant for Caudal Blockade in Pediatric Surgical Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Caudal block is commonly used to provide postoperative analgesia after pediatric surgery in the lower abdomen. Typically administered as a single-shot technique, 1 limitation of this block is the short duration of analgesia. To overcome this, dexamethasone has been used as an adjuvant to prolong block duration. However, there are concerns about steroid-related morbidity and the optimal route of dexamethasone administration (eg, caudal or intravenous) is unknown. METHODS: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials recruiting pediatric surgical patients receiving a caudal block for surgical anesthesia or postoperative analgesia. Included studies compared dexamethasone (caudal, intravenous, or both) to control. Duration of analgesia was the primary outcome. Database sources were Medline, Embase, the Cochrane Library, and Google Scholar searched up to August 18, 2017, without language restriction. Screening of studies, data extraction, and risk of bias assessment were performed independently and in duplicate by 2 authors. Risk of bias was assessed using Cochrane methodology and the strength of evidence was scored using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: The initial search retrieved 93 articles. Fourteen randomized controlled trials that comprised 1315 pediatric patients met the inclusion criteria. All but 1 study involved lower abdominal operations (orchidopexy, inguinal hernia repair, and hypospadias repair). The caudal and intravenous dose of dexamethasone ranged from 0.1 to 0.2 mg/kg and 0.5 to 1.5 mg/kg, respectively, and all studies were pooled in the main analysis. Dexamethasone prolonged the duration of analgesia by both the caudal route (5.43 hours, 95% confidence interval [CI], 3.52-7.35; P < .001; I = 99.3%; N = 9; n = 620; GRADE quality = moderate) and intravenous route (5.51 hours; 95% CI, 3.56-7.46; P < .001; I = 98.9%; N = 5; n = 364; GRADE quality = moderate) versus control. Secondary benefits of dexamethasone included reduced narcotic rescue analgesia requirement in the postanesthetic care unit (relative risk [RR], 0.30; 95% CI, 0.18-0.51; P < .001; I = 0.0%; N = 5; number needed to treat for benefit [NNTB] = 5; 95% CI, 4-7), less subsequent postoperative rescue analgesia requirement (RR, 0.46; 95% CI, 0.23-0.92; P = .03; I = 96.0%; N = 9; n = 629; NNTB = 3; 95% CI, 2-20; n = 310), and lower rates of postoperative nausea and vomiting (RR, 0.47; 95% CI, 0.30-0.73; P = .001; I = 0.0%; NNTB = 11; 95% CI, 8-21; N = 9; n = 628). Adverse events linked to the dexamethasone were rare. CONCLUSIONS: Caudal and intravenous dexamethasone are similarly effective for prolonging the duration of analgesia from caudal blockade, resulting in a doubled to tripled duration. Given the off-label status of caudal dexamethasone, intravenous administration is recommended-although only high intravenous doses (0.5 mg/kg up to 10 mg) have been studied.

Does goal-directed haemodynamic and fluid therapy improve peri-operative outcomes?: A systematic review and meta-analysis.

BACKGROUND: Much uncertainty exists as to whether peri-operative goal-directed therapy is of benefit. OBJECTIVES: To discover if peri-operative goal-directed therapy decreases mortality and morbidity in adult surgical patients. DESIGN: An updated systematic review and random effects meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase and the Cochrane Library were searched up to 31 December 2016. ELIGIBILITY CRITERIA: Randomised controlled trials enrolling adult surgical patients allocated to receive goal-directed therapy or standard care were eligible for inclusion. Trauma patients and parturients were excluded. Goal-directed therapy was defined as fluid and/or vasopressor therapy titrated to haemodynamic goals [e.g. cardiac output (CO)]. Outcomes included mortality, morbidity and hospital length of stay. Risk of bias was assessed using Cochrane methodology. RESULTS: Ninety-five randomised trials (11 659 patients) were included. Only four studies were at low risk of bias. Modern goal-directed therapy reduced mortality compared with standard care [odds ratio (OR) 0.66; 95% confidence interval (CI) 0.50 to 0.87; number needed to treat = 59; N = 52; I = 0.0%]. In subgroup analysis, there was no mortality benefit for fluid-only goal-directed therapy, cardiac surgery patients or nonelective surgery. Contemporary goal-directed therapy also reduced pneumonia (OR 0.69; 95% CI, 0.51 to 0. 92; number needed to treat = 38), acute kidney injury (OR 0. 73; 95% CI, 0.58 to 0.92; number needed to treat = 29), wound infection (OR 0.48; 95% CI, 0.37 to 0.63; number needed to treat = 19) and hospital length of stay (days) (-0.90; 95% CI, -1.32 to -0.48; I = 81. 2%). No important differences in outcomes were found for the pulmonary artery catheter studies, after accounting for advances in the standard of care. CONCLUSION: Peri-operative modern goal-directed therapy reduces morbidity and mortality. Importantly, the quality of evidence was low to very low (e.g. Grading of Recommendations, Assessment, Development and Evaluation scoring), and there was much clinical heterogeneity among the goal-directed therapy devices and protocols. Additional well designed and adequately powered trials on peri-operative goal-directed therapy are necessary.

Should Transfusion Trigger Thresholds Differ for Critical Care Versus Perioperative Patients? A Meta-Analysis of Randomized Trials.

OBJECTIVE: To address the significant uncertainty as to whether transfusion thresholds for critical care versus surgical patients should differ. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Medline, EMBASE, and Cochrane Library searches were performed up to 15 June 2016. PATIENTS: Trials had to enroll adult surgical or critically ill patients for inclusion. INTERVENTIONS: Studies had to compare a liberal versus restrictive threshold for the transfusion of allogeneic packed RBCs. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 30-day all-cause mortality, sub-grouped by surgical and critical care patients. Secondary outcomes included myocardial infarction, stroke, renal failure, allogeneic blood exposure, and length of stay. Odds ratios and weighted mean differences were calculated using random effects meta-analysis. To assess whether subgroups were significantly different, tests for subgroup interaction were used. Subgroup analysis by trials enrolling critically ill versus surgical patients was performed. Twenty-seven randomized controlled trials (10,797 patients) were included. In critical care patients, restrictive transfusion resulted in significantly reduced 30-day mortality compared with liberal transfusion (odds ratio, 0.82; 95% CI, 0.70-0.97). In surgical patients, a restrictive transfusion strategy led to the opposite direction of effect for mortality (odds ratio, 1.31; 95% CI, 0.94-1.82). The subgroup interaction test was significant (p = 0.04), suggesting that the effect of restrictive transfusion on mortality is statistically different for critical care (decreased risk) versus surgical patients (potentially increased risk or no difference). Regarding secondary outcomes, for critically ill patients, a restrictive strategy resulted in reduced risk of stroke/transient ischemic attack, packed RBC exposure, transfusion reactions, and hospital length of stay. In surgical patients, restrictive transfusion resulted in reduced packed RBC exposure. CONCLUSIONS: The safety of restrictive transfusion strategies likely differs for critically ill patients versus perioperative patients. Further trials investigating transfusion strategies in the perioperative setting are necessary.

Guidelines to the Practice of Anesthesia - Revised Edition 2018.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2018 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2018 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

Programmed intermittent peripheral nerve local anesthetic bolus compared with continuous infusions for postoperative analgesia: A systematic review and meta-analysis.

STUDY OBJECTIVE AND BACKGROUND: The role of the programmed intermittent bolus (PIB) technique for infusion of local anesthetics in continuous peripheral nerve blockade (CPNB) remains to be elucidated. Randomized controlled trials (RCTs) on PIB versus continuous infusion for CPNB have demonstrated conflicting results and no systematic review or meta-analysis currently exists. We aimed to delineate via systematic review with meta-analysis if there is any analgesic benefit to performing PIB versus continuous infusion for CPNB. DESIGN: We conducted a systematic review and random-effects meta-analysis of RCTs. DATA SOURCES: We searched Medline, Embase, and the Cochrane Library without language restriction from inception to 2-May-2017. ELIGIBILITY CRITERIA: Included RCTs had to compare PIB to continuous infusion in adult surgical patients receiving any upper or lower limb CPNB for postoperative analgesia. VAS pain scores were the primary outcome. The Cochrane Risk of Bias Tool with GRADE methodology was utilized to assess evidence quality. RESULTS: Nine RCTs (448 patients) met the inclusion criteria. Two studies performed upper limb blocks and the rest lower limb blocks. Five RCTs activated the CPNB with long-acting local anesthetic and only five used multi-modal analgesia. PIB modestly reduced VAS pain scores at 6h (-14.2mm; 95%CI -23.5mm to -5.0mm; I2=82.5%; p=0.003) and 12h (-9.9mm; 95%CI -14.4mm to -5.4mm; I2=12.4%; p<0.001), but not at later time points. There were no other meaningful differences in the rest of the outcomes, apart from more residual motor block with PIB (OR 4.27; 95% CI 1.08-16.9; p=0.04; NNTH=8). GRADE scoring ranged from low to very low. CONCLUSIONS: The existing evidence demonstrates that PIB does not meaningfully reduce VAS pain scores in CPNB. This systematic review provides important information about the limitations of existing studies. Future studies should reflect contemporary practice and focus on more painful operations.

Perineural Versus Intravenous Dexamethasone as an Adjuvant for Peripheral Nerve Blocks: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Dexamethasone is a useful adjuvant in regional anesthesia that is used to prolong the duration of analgesia for peripheral nerve blocks. Recent randomized controlled trials (RCTs) have demonstrated conflicting results as to whether perineural versus intravenous (IV) administration is superior in this regard, and the perineural use of dexamethasone remains off-label. Therefore, we sought to perform a systematic review and meta-analysis of RCTs. METHODS: In accordance with PRISMA guidelines, we performed a random-effects meta-analysis of RCTs comparing perineural versus IV dexamethasone with duration of analgesia as the primary outcome. RESULTS: Eleven RCTs met the inclusion criteria with a total of 1076 subjects. Perineural dexamethasone prolonged the duration of analgesia by 3.77 hours (95% confidence interval [CI], 1.87-5.68 hours; P < 0.001) compared to IV dexamethasone, with high statistical heterogeneity. For secondary outcomes, perineural dexamethasone prolonged the duration of both motor (3.47 hours [95% CI, 1.49-5.45]; P < 0.001) and sensory (2.28 hours [95% CI, 0.38-4.17]; P = 0.019) block compared to IV administration. Furthermore, perineural dexamethasone patients consumed slightly less oral opioids at 24 hours than IV dexamethasone patients (7.1 mg of oral morphine equivalents [95% CI, 0.74-13.5 mg]; P = 0.029), and there were no statistically significant differences in the other secondary outcomes. Notably, no increase in adverse events was detected. CONCLUSIONS: Perineural dexamethasone prolongs the duration of analgesia across the RCTs included in our meta-analysis. The magnitude of effect of 3.77 hours raises the question as to whether perineural dexamethasone should be administered routinely over its IV counterpart-or reserved for selected patients where such prolongation would be clinically important.

Guidelines to the Practice of Anesthesia - Revised Edition 2017.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2017 (the guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. Because the guidelines are subject to revision, updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2017 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the society cannot guarantee any specific patient outcome. Each anesthesiologist should exercise his or her own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

Liquid-body resonance while contacting a rotating superhydrophobic surface.

We advance a scheme in which a liquid body on a stationary tip in contact with a rotating superhydrophobic surface is able to maintain resonance primarily from stick-slip events. With tip-to-surface spacing in the range 2.73 ≤ h < 2.45 mm for a volume of 10 µL, the liquid body was found to exhibit resonance independent of the speed of the drum. The mechanics were found to be due to a surface-tension-controlled vibration mode based on the natural frequency values determined. With spacing in the range 2.45 ≤ h < 2.15 mm imposed for a volume of 10 µL, the contact length of the liquid body was found to vary with rotation of the SH drum. This was due to the stick-slip events being able to generate higher energy fluctuations causing the liquid-solid contact areas to vary since the almost oblate spheroid shape of the liquid body had intrinsically higher surface energies. This resulted in the natural frequency perturbations being frequency- and amplitude-modulated over a lower frequency carrier. These findings have positive implications for microfluidic sensing.

What epidural opioid results in the best analgesia outcomes and fewest side effects after surgery?: a meta-analysis of randomized controlled trials.

BACKGROUND: Epidural opioids are widely used for central neuraxial blockade and postoperative analgesia. However, differences in analgesic efficacy and side effect rates among individual opioids remain controversial. METHODS: We conducted a random-effects meta-analysis of randomized controlled trials that compared at least 2 continuous epidural infusions for acute postoperative analgesia over at least 24 hours. Individual study data were weighted by the inverse-variance method. Visual analog scale (VAS) pain scores were the primary outcome. Secondary outcomes included opioid side effects, such as pruritus, postoperative nausea and vomiting (PONV), sedation, hypotension, and respiratory depression. RESULTS: Nineteen of the 24 trials included compared 2 of the following opioids: morphine, fentanyl, or sufentanil. The total subjects studied were 1513. Pooled analysis by type of surgery showed no clinically significant differences in VAS pain scores at any time after surgery. There were more PONV (OR = 1.91; 95% CI, 1.14-3.18; P = 0.014) and perhaps pruritus (OR = 1.64; 95% CI, 0.98-2.76; P = 0.162) with morphine compared to fentanyl. Total opioid consumption differed only in the trials comparing morphine and fentanyl, where patients in the morphine group required 1.2 mg (of morphine equivalent) less (95% CI, 0.27-2.18). Use of analgesic adjuncts was similar for all but 2 studies. CONCLUSIONS: Analgesic outcome, in terms of VAS pain score, was similar between the epidural opioids studied. These similarities in analgesia may reflect the common practices of concurrently using epidural local anesthetics with the opioids and titrating infusion rates according to a patient's pain status. With respect to side effects, the incidence of PONV and possibly pruritus was higher with morphine compared with fentanyl, despite there being similar total opioid consumption between those groups.

Small-molecule modulators of Listeria monocytogenes biofilm development.

Listeria monocytogenes is an important food-borne pathogen whose ability to form disinfectant-tolerant biofilms on a variety of surfaces presents a food safety challenge for manufacturers of ready-to-eat products. We developed here a high-throughput biofilm assay for L. monocytogenes and, as a proof of principle, used it to screen an 80-compound protein kinase inhibitor library to identify molecules that perturb biofilm development. The screen yielded molecules toxic to multiple strains of Listeria at micromolar concentrations, as well as molecules that decreased (≤ 50% of vehicle control) or increased (≥ 200%) biofilm formation in a dose-dependent manner without affecting planktonic cell density. Toxic molecules-including the protein kinase C antagonist sphingosine-had antibiofilm activity at sub-MIC concentrations. Structure-activity studies of the biofilm inhibitory compound palmitoyl-d,l-carnitine showed that while Listeria biofilm formation was inhibited with a 50% inhibitory concentration of 5.85 ± 0.24 µM, d,l-carnitine had no effect, whereas palmitic acid had stimulatory effects. Saturated fatty acids between C(9:0) and C(14:0) were Listeria biofilm inhibitors, whereas fatty acids of C(16:0) or longer were stimulators, showing chain length specificity. De novo-synthesized short-chain acyl carnitines were less effective biofilm inhibitors than the palmitoyl forms. These molecules, whose activities against bacteria have not been previously established, are both useful probes of L. monocytogenes biology and promising leads for the further development of antibiofilm strategies.

Palmitoyl-DL-carnitine is a multitarget inhibitor of Pseudomonas aeruginosa biofilm development.

Bacteria growing in biofilms are often in metabolic and physiological states that do not respond well to antibiotics, and thus, are major contributors to chronic diseases. Biofilm inhibitors, therefore, have the potential to be used alone or as adjuvants to conventional antibiotic therapies. Here, we screened a chemically diverse collection of protein kinase inhibitors for molecules that perturb biofilm development. Among the inhibitory molecules identified, palmitoyl-DL-carnitine (pDLC) impaired Pseudomonas aeruginosa and Escherichia coli biofilm formation in a dose-dependent manner. The pDLC affected multiple pathways implicated in P. aeruginosa biofilm development; it stimulated motility, inhibited activity of the Las quorum sensing system, and overrode the biofilm-promoting effects of subminimal inhibitory concentrations of aminoglycosides and high levels of the second messenger, cyclic-di-GMP. Palmitic acid, but not carnitine, inhibited biofilm formation but did not stimulate motility, suggesting that pDLC works through unique mechanisms. The ability to target multiple pathways involved in biofilm formation is desirable in an inhibitor, which makes pDLC an interesting lead for antibiofilm therapies.