Association Between Race and Opioid-Induced Respiratory Depression: An International Post Hoc Analysis of the Prediction of Opioid-induced Respiratory Depression In Patients Monitored by Capnography Trial.

BACKGROUND: Opioid-induced respiratory depression (OIRD) is common on the medical and surgical wards and is associated with increased morbidity and health care costs. While previous studies have investigated risk factors for OIRD, the role of race remains unclear. We aim to investigate the association between race and OIRD occurrence on the medical/surgical ward. METHODS: This is a post hoc analysis of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial; a prospective multinational observational blinded study of 1335 general ward patients who received parenteral opioids and underwent blinded capnography and oximetry monitoring to identify OIRD episodes. For this study, demographic and perioperative data, including race and comorbidities, were analyzed and assessed for potential associations with OIRD. Univariable χ 2 and Mann-Whitney U tests were used. Stepwise selection of all baseline and demographic characteristics was used in the multivariable logistic regression analysis. RESULTS: A total of 1253 patients had sufficient racial data (317 Asian, 158 Black, 736 White, and 42 other races) for inclusion. The incidence of OIRD was 60% in Asians (N = 190/317), 25% in Blacks (N = 40/158), 43% in Whites (N = 316/736), and 45% (N = 19/42) in other races. Baseline characteristics varied significantly: Asians were older, more opioid naïve, and had higher opioid requirements, while Blacks had higher incidences of heart failure, obesity, and smoking. Stepwise multivariable logistic regression revealed that Asians had increased risk of OIRD compared to Blacks (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.54-4.04; P = .0002) and Whites (OR, 1.38; 95% CI, 1.01-1.87; P = .0432). Whites had a higher risk of OIRD compared to Blacks (OR, 1.81; 95% CI, 1.18-2.78; P = .0067). The model's area under the curve was 0.760 (95% CI, 0.733-0.787), with a Hosmer-Lemeshow goodness-of-fit test P value of .23. CONCLUSIONS: This post hoc analysis of PRODIGY found a novel association between Asian race and increased OIRD incidence. Further study is required to elucidate its underlying mechanisms and develop targeted care pathways to reduce OIRD in susceptible populations.

A BEME systematic review of teaching interventions to equip medical students and residents in early recognition and prompt escalation of acute clinical deteriorations: BEME Guide No. 62.

Background: Current educational interventions and teaching for acute deteriorations seem to address acute care learning in discreet segments. Technology enhanced and team training methodologies are in vogue though well studied in the nursing profession, teaching avenues for junior 'doctors in training' seem to be a lacuna.Aims: The BEME systematic review was designed to (1) appraise the existing published evidence on educational interventions that are intended for 'doctors in training' to teach early recognition and prompt escalation in acute clinical deteriorations (2) to synthesise evidence & to evaluate educational effectiveness.Methodology: The method applied was a descriptive, justification & clarification review. Databases searched included PubMed, PsycINFO, Science Direct and Scopus for original research and grey literature with no restrictions to year or language. Abstract review, full text decisions and data extraction were completed by two primary coders with final consensus by a third reviewer.Results: 5592 titles and abstracts were chosen after removal of 905 duplications. After exclusion of 5555 studies, 37 full text articles were chosen for coding. 22 studies met final criteria of educational effectiveness, relevance to acute care. Educational platforms varied from didactics to blended learning approaches, small group teaching sessions, simulations, live & cadaveric tissue training, virtual environments and insitu team-based training. Translational outcomes with reduction in long term (up to 3-6 years) morbidity & mortality with financial savings were reported by 18% (4/22) studies. Interprofessional training were reported in 41% (9/22) of studies. Recent evidence demonstrated effectiveness of virtual environment and mobile game-based learning.Conclusions: There were significant improvements in teaching initiatives with focus on observable behaviours and translational real patient outcomes. Serious game-based learning and virtual multi-user collaborative environments might enhance individual learners' cognitive deliberate practice. Acute care learning continuum with programmatic acute care portfolios could be a promise of the future.

Neurologic and cognitive outcomes associated with the clinical use of xenon: a systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: Xenon has been shown to have positive neurologic effects in various pre-clinical models. This study systematically reviewed the randomized-controlled trials (RCTs) investigating neurologic and cognitive outcomes associated with the clinical use of xenon. METHODS: We searched PubMed, CENTRAL, EMBASE, CINAHL, elibrary.ru (for Russian studies), Google Scholar (for Russian studies), and Wanfang (for Chinese studies) for appropriate RCTs comparing neurologic or cognitive outcomes after clinical use of xenon with control treatment or with other anesthetic agents. RESULTS: Seventeen RCTs met the inclusion criteria. Two studies investigated the effects of xenon plus therapeutic hypothermia to treat neonatal asphyxia or out-of-hospital cardiac arrest. Compared with therapeutic hypothermia alone, xenon and therapeutic hypothermia reduced cerebral white matter abnormalities after cardiac arrest but had no effect on neurocognitive outcome and mortality. Xenon had no added value when used to treat neonatal asphyxia. Thirteen RCTs compared neurocognitive effects of xenon with other anesthetic agents in surgical patients. While xenon may be associated with improved short-term (< three hours) cognitive outcome, no medium-term (six hours to three months) advantage was observed, and longer-term data are lacking. No differences in biochemical (S-100ß, neuron-specific enolase) and neuropsychologic (attentional performance) outcomes were found with xenon compared with other anesthetic drugs. Finally, two studies suggest that brief, intermittent administration of sub-anesthetic doses of xenon to patients during the acute phase of substance withdrawal may improve neurocognitive outcomes. CONCLUSIONS: Despite promising pre-clinical results, the evidence for positive clinical neurologic and cognitive outcomes associated with xenon administration is modest. Nevertheless, there is some evidence to suggest that xenon may be associated with better neurologic outcomes compared with the standard of care therapy in certain specific clinical situations. More clinical trials are needed to determine any potential benefit linked to xenon administration.

Xenon Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Xenon anesthesia has been studied for decades. However, no meta-analysis of randomized controlled trials (RCTs) on xenon anesthesia has been conducted. The aim of this study was to systematically review all available evidence from RCTs comparing xenon and other inhaled and IV anesthetics on anesthetic outcomes. Our meta-analysis attempted to quantify the effects of xenon anesthesia on clinical outcomes in relation to other anesthetics. METHODS: We found 43 RCTs from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL (until January 2015). A total of 31 studies comparing xenon (841 patients) with other inhaled agents (836 patients) and 12 studies comparing xenon (373 patients) with propofol (360 patients) were found. We evaluated clinical outcomes, such as intraoperative hemodynamics, emergence, and postoperative nausea and vomiting (PONV). RESULTS: Patients undergoing xenon anesthesia had a lower heart rate and higher mean arterial pressure (MAP) intraoperatively than those receiving volatile anesthesia (mean difference = -6 min⁻¹ [99% confidence interval {99% CI} -10.0 to -2.3]; mean difference = 9 mm Hg [99% CI 3.1-14.4]) and propofol anesthesia (mean difference = -10 min⁻¹ [99% CI -12.4 to -6.6]; mean difference = 7 mm Hg [99% CI 0.85-13.2]). Compared with baseline, intraoperative MAP remained relatively stable (change < 5.5%, 99% CI within ±20% of the baseline) under xenon anesthesia, but MAP decreased by ≥15% under volatile (mean difference = -17 mm Hg [99% CI -29.5 to - 4.9], percentage change = -17.5%) and propofol (mean difference = -14 mm Hg [99% CI -26.1 to -2.5], percentage change = -15.0%) anesthesia. Patients had faster emergence from xenon than from volatile anesthesia: eyes opening (versus all volatile agents: mean 4 vs 7 minutes, percentage change = -49.8% [99% CI -55.1% to -44.0%]), tracheal extubation (versus all volatile agents: mean 4 vs 8 minutes percentage change = -44.6% [99% CI -57.3% to -28.1%]), orientation (versus sevoflurane: mean 5 vs 10 minutes, percentage change = -45.1% [99% CI -58.5% to -28.1%]), countdown (versus sevoflurane: mean 6 vs 10 minutes, percentage change = -41.7% [99% CI -50.3% to -31.6%]; versus isoflurane: mean 6 vs 14 minutes, percentage change = -57.7% [99% CI -65.7% to -48.3%]), and reaction on demand (versus sevoflurane: mean 4 vs 8 minutes, percentage change = -53.2% [99% CI -65.7% to -35.6%]). However, xenon anesthesia increased the risks of PONV (incidence 34.4% vs 19.9%; risk ratio = 1.72 [99% CI 1.10-2.69], risk difference = 0.19 [99% CI 0.04-0.33]). CONCLUSIONS: Xenon anesthesia provides relatively more stable intraoperative blood pressure, lower heart rate, and faster emergence from anesthesia than volatile and propofol anesthesia. However, xenon is associated with a higher incidence of PONV.

Paravertebral Block for Inguinal Herniorrhaphy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Paravertebral block (PVB) is a safe and effective anesthetic technique for thoracotomy and mastectomy. However, no systematic review or meta-analysis has focused on PVB for inguinal herniorrhaphy. Our study compares PVB with general anesthesia/systemic analgesia, neuraxial blocks, and other peripheral nerve blocks. METHODS: We analyzed 14 randomized controlled trials from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL up to February 2015, without language restriction, comparing PVB under sedation with general anesthesia/systematic analgesia (135 vs 133 patients), neuraxial blocks (191 vs 186 patients), and other peripheral nerve blocks (119 vs 117 patients). We investigated pain scores, consumption of postoperative analgesia, incidence of postoperative nausea and vomiting (PONV), length of hospital stay, postanesthesia care unit bypassing rate, time to perform blocks, intraoperative hemodynamics, and incidence of urinary retention. Joint hypothesis testing was adopted for pain and analgesics, PONV, and hemodynamic variables. All analyses were performed with RevMan 5.2.11 (Cochrane Collaboration, Copenhagen). Hartung-Knapp-Sidik-Jonkman method was used for post hoc testing. RESULTS: PVB reduced PONV (nausea: risk ratio [RR] = 0.22; 95% confidence interval [CI], 0.05-0.93; numbers needed to treat [NNT] = 4.5; I = 15% and vomiting: RR = 0.15; 95% CI, 0.03-0.76; NNT = 8.3; I = 0%) compared with general anesthesia/systematic analgesia (quality of evidence [QoE]: high). Compared with neuraxial blocks, PVB resulted in less postoperative nausea (RR = 0.34 [95% CI, 0.13-0.91], NNT = 8.3, I = 0%) and urinary retention (RR = 0.14 [95% CI, 0.05-0.42], NNT = 7.4, I = 0%) than neuraxial blocks (QoE: high). More time was needed to perform PVB than neuraxial blocks (standardized mean difference = 1.90 [95% CI, 0.02-3.77], I = 92%; mean difference = 5.33 minutes; QoE: moderate). However, the available data could not reject the null hypothesis of noninferiority on all pain scores and analgesic requirements for both PVB versus general anesthesia/systematic analgesia and PVB versus neuraxial blocks (QoE: low), as well as on hemodynamic outcomes for PVB versus neuraxial blocks (QoE: moderate). Our systematic review showed that PVB decreased postoperative pain scores and analgesic requirement as compared with ilioinguinal block and transversus abdominis plane block. CONCLUSIONS: This meta-analysis shows that PVB provides an anesthesia with fewer undesirable effects for inguinal herniorrhaphy. The choice between general anesthesia/systematic analgesia, neuraxial blocks, PVB, and other peripheral nerve blocks should be based on time available to perform the block and a complete coverage over the relevant structures by the blocks.

Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways.

PURPOSE: The optimal management of postoperative pain using multimodal analgesia is a key component of Enhanced Recovery After Surgery (ERAS). Pain has adverse clinical implications on postoperative recovery, including prolonging the time to recovery milestones and length of hospital stay. Moreover, the ubiquity of opioids in postoperative analgesic regimens results in adverse effects, such as sedation, postoperative nausea and vomiting, urinary retention, ileus, and respiratory depression, which can delay discharge. Thus, multimodal analgesia, i.e., the use of more than one analgesic modality to achieve effective pain control while reducing opioid-related side effects, has become the cornerstone of enhanced recovery. The purpose of this review is to address the analgesic techniques used as part of multimodal analgesic regimens to optimize postoperative pain control and to summarize the evidence for their use in reducing opioid requirements and side effects. PRINCIPAL FINDINGS: There is a wide variety of analgesic techniques available for multimodal postoperative analgesia. These modalities are divided into pharmacological and non-pharmacological techniques. Systemic pharmacological modalities involve opioids and non-opioids such as acetaminophen, non-steroidal anti-inflammatory drugs, N-methyl-D-aspartate receptor antagonists, anticonvulsants (e.g., gamma-aminobutyric acid analogues), beta-blockers, alpha-2 agonists, transient receptor potential vanilloid receptor agonists (capsaicin), and glucocorticoids. Other pharmacological modalities include central neuraxial techniques, surgical-site infiltration, and regional anesthesia. Evidence supports the use of these pharmacological techniques as part of multimodal analgesia, but each has its own advantages and specific safety profile, which highlights the importance of selecting the appropriate analgesics for each patient. Adjunctive non-pharmacological techniques include acupuncture, music therapy, transcutaneous electrical nerve stimulation, and hypnosis. There is mixed evidence regarding such techniques, although a lack of harm is associated with their use. CONCLUSION: There are continuing advancements in multimodal analgesic techniques; however, postoperative pain in general continues to be undermanaged. Furthermore, a continuing challenge in multimodal pain research related to ERAS is the difficulty in carrying out randomized trials to determine the relative importance of any one component, including analgesia.

Factors associated with international humanitarian aid appeal for disasters from 1995 to 2015: A retrospective database study.

INTRODUCTION: International humanitarian aid during disasters should be needs-based and coordinated in response to appeals from affected governments. We identify disaster and population factors associated with international aid appeal during disasters and hence guide preparation by international humanitarian aid providers. METHODS: In this retrospective database analysis, we searched the Emergency Events Database for all disasters from 1995 to 2015. Disasters with and without international aid appeals were compared by location, duration, type of disaster, deaths, number of people affected, and total estimated damage. Logistic regression was used to examine the association of each factor with international aid appeal. RESULTS: Of 13,961 disasters recorded from 1995 to 2015, 168 (1.2%) involved international aid appeals. Aid appeals were more likely to be triggered by disasters which killed more people (OR 1.29 [95% confidence interval (CI) 1.02-1.64] log10 persons), affected more people (OR 1.85 [95%CI 1.57-2.18] / log10 persons), and occurred in Africa (OR 1.67 [95%CI 1.06-2.62). Earthquakes (OR 4.07 [95%CI 2.16-7.67]), volcanic activity (OR 6.23 [95%CI 2.50-15.53]), and insect infestations (OR 12.14 [95%CI 3.05-48.35]) were more likely to trigger international aid appeals. International aid appeals were less likely to be triggered by disasters which occurred in Asia (OR 0.46 [95%CI 0.29-0.73]) and which were transport accidents (OR 0.12 [95%CI 0.02-0.89]). CONCLUSION: International aid appeal during disasters was associated with greater magnitude of damage, disasters in Africa, and specific types of disasters such as earthquakes, volcanic activity, and insect infestations. Humanitarian aid providers can focus preparation on these identified factors.

Systemic sclerosis is an independent risk factor for increased coronary artery calcium deposition.

OBJECTIVE: Endothelial dysfunction and inflammation are pathogenic mechanisms common to systemic sclerosis (SSc) and atherosclerosis. This study was undertaken to examine the relationship between coronary atherosclerosis, as assessed by the coronary artery calcium score (CACS), and conventional cardiovascular and disease-specific risk factors in SSc patients. METHODS: The CACS was measured by computed tomography, and cardiovascular risk factors were examined in SSc patients and compared with controls matched for age, sex, and glycemic status. Disease activity score, antiphospholipid antibodies, high-sensitivity C-reactive protein level, and erythrocyte sedimentation rate were measured in SSc patients. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined. RESULTS: We recruited 53 SSc patients (50 women and 3 men) and 106 controls. The patients had a mean ± SD age of 53.1 ± 12.9 years and a median disease duration of 9 years. Compared to controls, SSc patients had significantly lower low-density lipoprotein (LDL) cholesterol levels (P = 0.001), high-density lipoprotein cholesterol levels (P = 0.01), diastolic blood pressure, waist circumference, and body mass index and were more likely to be receiving vasodilators (all P < 0.001). There was a significantly higher proportion of SSc patients among subjects with more severe coronary calcification (CACS ≥ 101) compared to those with lesser severity (CACS <100) (56.5% versus 29.4%; P = 0.01). Multiple logistic regression analysis revealed SSc to be an independent determinant for a CACS ≥ 101 (OR 10.89 [95% CI 2.21-53.75], P = 0.003) together with age and LDL cholesterol level after adjustment for other cardiovascular risk factors. Among disease-specific factors, only disease duration (OR 1.14 [95% CI 1.02-1.27], P = 0.02) was independently associated with more severe coronary calcification (CACS ≥ 101). CONCLUSION: Our findings indicate that SSc is an independent risk factor for coronary calcification, in addition to the conventional risk factors for coronary atherosclerosis, such as age and hypertension.

Changes of Drug Pharmacokinetics in Patients with Short Bowel Syndrome: A Systematic Review.

BACKGROUND AND OBJECTIVES: Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a loss of absorptive surfaces, the absorption of orally administered drugs is also often affected. The purpose of this study was to systematically review the published literature and examine the effects of short bowel syndrome on drug pharmacokinetics and clinical outcomes. METHODS: Studies were identified through searches of databases MEDLINE, EMBASE, Web of Science, and SCOPUS, in addition to hand searches of studies' reference lists. Two reviewers independently assessed studies for inclusion, yielding 50 studies involving 37 different drugs in patients with short bowel syndrome. RESULTS: Evidence of decreased drug absorption was observed in 29 out of 37 drugs, 6 of which lost therapeutic effect, and 14 of which continued to demonstrate clinical benefit through drug monitoring. CONCLUSIONS: The influence of short bowel syndrome on drug absorption appears to be drug-specific and dependent on the location and extent of resection. The presence of a colon in continuity may also influence drug bioavailability as it can contribute significantly to the absorption of drugs (e.g., metoprolol); likewise, drugs that have a wide absorption window or are known to be absorbed in the colon are least likely to be malabsorbed. Individualized dosing may be necessary to achieve therapeutic efficacy, and therapeutic drug monitoring, where available, should be considered in short bowel syndrome patients, especially for drugs with narrow therapeutic indices.

Factors reducing inappropriate attendances to emergency departments before and during the COVID-19 pandemic: A multicentre study.

INTRODUCTION: Inappropriate attendances (IAs) to emergency departments (ED) create an unnecessary strain on healthcare systems. With decreased ED attendance during the COVID-19 pandemic, this study postulates that there are less IAs compared to before the pandemic and identifies factors associated with IAs. METHODS: We performed a retrospective review of 29,267 patient presentations to a healthcare cluster in Singapore from 7 April 2020 to 1 June 2020, and 36,370 patients within a corresponding period in 2019. This time frame coincided with local COVID-19 lockdown measures. IAs were defined as patient presentations with no investigations required, with patients eventually discharged from the ED. IAs in the 2020 period during the pandemic were compared with 2019. Multivariable logistic regression was performed to identify factors associated with IAs. RESULTS: There was a decrease in daily IAs in 2020 compared to 2019 (9.91±3.06 versus 24.96±5.92, P<0.001). IAs were more likely with self-referrals (adjusted odds ratio [aOR] 1.58, 95% confidence interval [CI] 1.50-1.66) and walk-ins (aOR 4.96, 95% CI 4.59-5.36), and those diagnosed with non-specific headache (aOR 2.08, 95% CI 1.85-2.34), or non-specific low back pain (aOR 1.28, 95% CI 1.15-1.42). IAs were less likely in 2020 compared to 2019 (aOR 0.67, 95% CI 0.65-0.71) and older patients (aOR 0.79 each 10 years, 95% CI 0.78-0.80). CONCLUSION: ED IAs decreased during COVID-19. The pandemic has provided a unique opportunity to examine factors associated with IAs.

Undertreatment of osteoporosis following hip fracture: a retrospective, observational study in Singapore.

Undertreatment of osteoporosis after hip fracture increases the risk of death, disability, recurrent osteoporotic fractures, and financial burden. Only half were compliant with osteoporosis medications. Elderly patients were less persistent and compliant to treatment. Denosumab was associated with a higher proportion of days covered by osteoporosis medications than oral bisphosphonates. PURPOSE: The aim of this study was to identify factors that contributed to the initiation of osteoporosis medications following hip fracture as well as the compliance and persistence to osteoporosis medications. METHODS: Clinical data of 532 patients older than 50 years old admitted for surgical fixation of hip fractures were reviewed. Three hundred forty-seven had sufficient data for analysis after excluding patients with non-fragility fractures. Prescription for any osteoporosis medication in the year following hip fracture as well as compliance to treatment was evaluated. RESULTS: Only 40.3% of patients were prescribed with osteoporosis medication within 1 year post-hip fracture. Females (p = 0.020) performing dual-energy x-ray absorptiometry scan (p < 0.001) and 25 hydroxyvitamin D levels testing post-hip fracture (p < 0.027) were independent determinants of increased likelihood of being prescribed with osteoporosis medication. Patients with proportion of days covered (PDC) ≥ 0.8 (or 80% of days covered in a year) were defined as compliant. Overall, only 49.7% of the patients were compliant with osteoporosis medications. Elderly patients aged 70-79 years (p = 0.002) and males (p = 0.017) were less persistent with osteoporosis treatment when compared with patients aged < 69 years and females. The compliance was poorer in patients aged 70-79 years (p = 0.026) as compared with those under 69 years of age. Statistically significant difference (p = 0.032) was observed between mean PDC of oral bisphosphonates (0.66) and denosumab (0.83). Only 39.3% of patients were persistent with treatment at 1 year. CONCLUSION: Our findings demonstrate the urgent need to increase awareness through a structured protocol of osteoporosis treatment. A multi-disciplinary Fracture Liaison Service should be set up to ensure compliance to osteoporosis medication post-hip fracture.

Lidocaine patch for acute pain management: a meta-analysis of prospective controlled trials.

BACKGROUND: Local anesthetic is one of the cornerstones of multimodal analgesia. We investigated the efficacy of the lidocaine patch for acute pain management. METHODS: We searched MEDLINE, CINAHL, Scopus, and the Cochrane Controlled Trials Register for published prospective controlled clinical trials that evaluated the analgesic effect of the lidocaine patch for acute or postoperative pain management (1966--2014). The outcomes were postoperative opioid consumption, pain intensity and length of hospital stay. RESULTS: Five trials comparing the lidocaine patch with control (no treatment/placebo) for acute or postoperative pain treatment/management were included in this meta-analysis. Data was analyzed on 251 patients. Between the lidocaine patch group and the control group, no significant difference was found for all three outcomes (all p > 0.05). For postoperative opioid consumption, mean difference (MD) was -8.2 mg morphine equivalent (95% CI -28.68, 12.24). For postoperative pain intensity, MD was -9.1 mm visual analog scale or equivalent (95% CI -23.31, 5.20). For length of hospital stay, MD was -0.2 days (95% CI -0.80, 0.43). CONCLUSION: Application of a lidocaine patch may not be an effective adjunct for acute and postoperative pain management, in terms of pain intensity, opioid consumption and length of hospital stay. LIMITATIONS: The limitations were a small number of included studies, potential biases from some unblinded studies, clinical heterogeneity between studies, and incomplete reported data for adjunct analgesics.