Regional anaesthesia quality indicators for adult patients undergoing non-cardiac surgery: a systematic review.

Improvement in healthcare delivery depends on the ability to measure outcomes that can direct changes in the system. An overview of quality indicators within the field of regional anaesthesia is lacking. This systematic review aims to synthesise available quality indicators, as per the Donabedian framework, and provide a concise overview of evidence-based quality indicators within regional anaesthesia. A systematic literature search was conducted using the databases MEDLINE, Embase, CINAHL and Cochrane from 2003 to present, and a prespecified search of regional anaesthesia society websites and healthcare quality agencies. The quality indicators relevant to regional anaesthesia were subdivided into peri-operative structure, process and outcome indicators as per the Donabedian framework. The methodological quality of the indicators was determined as per the Oxford Centre for Evidence-Based Medicine's framework. Twenty manuscripts met our inclusion criteria and, in total, 68 unique quality indicators were identified. There were 4 (6%) structure, 12 (18%) process and 52 (76%) outcome indicators. Most of the indicators were related to the safety (57%) and effectiveness (19%) of regional anaesthesia and were general in nature (60%). In addition, most indicators (84%) were based on low levels of evidence. Our study is an important first step towards describing quality indicators for the provision of regional anaesthesia. Future research should focus on the development of structure and process quality indicators and improving the methodological quality and usability of these indicators.

Non-opioid analgesic modes of pain management are associated with reduced postoperative complications and resource utilisation: a retrospective study of obstructive sleep apnoea patients undergoing elective joint arthroplasty.

BACKGROUND: Studies on the effectiveness of multimodal analgesia, particularly in patients at higher perioperative risk from obstructive sleep apnoea (OSA), are lacking. We aimed to assess the impact of multimodal analgesia on opioid use and complications in this high-risk cohort. METHODS: We conducted a population-based retrospective cohort study of OSA patients undergoing elective lower extremity joint arthroplasty (2006-16, Premier Healthcare database). Multimodal analgesia was defined as opioid use with the addition of one, two, or more non-opioid analgesic modes including, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, paracetamol/acetaminophen, peripheral nerve blocks, steroids, gabapentin/pregabalin, or ketamine. Multilevel multivariable regression models measured associations between multimodal analgesia and opioid prescription (primary outcome; oral morphine equivalents). Secondary outcomes included opioid- and OSA-related complications, and resource utilisation. Odds ratios (OR) or % change and 95% confidence intervals (CI) are reported. RESULTS: Among 181 182 OSA patients included, 88.5% (n = 160 299) received multimodal analgesia with increasing utilisation trends. Multivariable models showed stepwise beneficial postoperative outcome effects with increasing additional analgesic modes compared with opioid-only analgesia. In patients who received more than two additional analgesia modes (n = 64 174), opioid dose prescription decreased by 14.9% (CI -17.0%; -12.7%), while odds were significantly decreased for gastrointestinal complications (OR 0.65, CI 0.53; 0.78), mechanical ventilation (OR 0.23, CI 0.16; 0.32), and critical care admission (OR 0.60, CI 0.48; 0.75), all P<0.0001. CONCLUSIONS: In a population at high risk for perioperative complications from OSA, multimodal analgesia was associated with a stepwise reduction in opioid use and complications, including critical respiratory failure.

Neuraxial anaesthesia techniques and postoperative outcomes among joint arthroplasty patients: is spinal anaesthesia the best option?

BACKGROUND: Neuraxial anaesthesia is frequently used for lower limb arthroplasty but it is unclear whether benefits vary among patients receiving different subtypes of neuraxial anaesthesia. We evaluated whether differences in risk for adverse postoperative outcomes exist between patients receiving combined spinal and epidural (CSE), epidural, or spinal anaesthesia. METHODS: In this retrospective cohort study, we identified 40 852 patients who underwent total hip and knee arthroplasty (THA and TKA) procedures under neuraxial anaesthesia (34 301 CSE, 2464 epidural, 4087 spinal) between 2005 and 2014 at a single institution. We used multivariable logistic regression to evaluate the following outcomes: cardiac, pulmonary, gastrointestinal, renal/genitourinary, and thromboembolic complications, and prolonged length of stay. RESULTS: Compared with CSE, spinal anaesthesia was associated with reduced adjusted odds for cardiac [odds ratio (OR), 0.68; 95% confidence interval (CI), 0.52-0.89], pulmonary (OR: 0.51; 95% CI: 0.38-0.68), gastrointestinal (OR: 0.50; 95% CI: 0.32-0.78), and thromboembolic complications (OR: 0.40; 95% CI: 0.23-0.73), and prolonged length of stay (OR: 0.72; 95% CI: 0.66-0.80). Patients who received epidural anaesthesia did not have significantly different odds for any outcomes compared with CSE patients. CONCLUSIONS: We identified clear differences in risk for certain postoperative events by subtype of neuraxial anaesthesia, suggesting that spinal anaesthesia is associated with the most favourable outcomes profile.

Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors.

BACKGROUND: Postoperative delirium continues to pose major clinical difficulties. While unmodifiable factors (e.g. age and comorbidity burden) are commonly studied risk factors for delirium, the role of modifiable factors, such as anaesthesia type and commonly used perioperative medications, remains understudied. This study aims to evaluate the role of modifiable factors for delirium after hip and knee arthroplasties. METHODS: We performed a retrospective study of 41 766 patients who underwent hip or knee arthroplasties between 2005 and 2014 at a single institution. Data were collected as part of routine patient care. Multivariable logistic regression models assessed associations between anaesthesia type and commonly used perioperative medications (opioids, benzodiazepines, and ketamine) and postoperative delirium. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Various sensitivity analyses are also considered, including multiple imputation methods to address missing data. RESULTS: Postoperative delirium occurred in 2.21% (n=922) of all patients. While patients who received neuraxial anaesthesia were at lower risk for postoperative delirium (compared with general anaesthesia; epidural OR 0.59 CI 0.38-0.93; spinal OR 0.55 CI 0.37-0.83; combined spinal/epidural OR 0.56 CI 0.40-0.80), those given intraoperative ketamine (OR 1.27 CI 1.01-1.59), opioids (OR 1.25 CI 1.09-1.44), postoperative benzodiazepines (OR 2.47 CI 2.04-2.97), and ketamine infusion (OR 10.59 CI 5.26-19.91) were at a higher risk. CONCLUSIONS: In this cohort of hip and knee arthroplasty patients, anaesthesia type and perioperative medications were associated with increased odds for postoperative delirium. Our results support the notion that modifiable risk factors may exacerbate or attenuate risk for postoperative delirium.

Epidemiology, trends, and disparities in regional anaesthesia for orthopaedic surgery.

Recent studies have linked the use of regional anaesthesia to improved outcomes. Epidemiological research on utilization, trends, and disparities in this field is sparse; however, large nationally representative database constructs containing anaesthesia-related data, demographic information, and multiyear files are now available. Together with advances in research methodology and technology, these databases provide the foundation for epidemiological research in anaesthesia. We present an overview of selected studies that provide epidemiological data and describe current anaesthetic practice, trends, and disparities in orthopaedic surgery in particular. This literature suggests that that even among orthopaedic surgical procedures, which are highly amenable to regional anaesthetic techniques, neuraxial anaesthetics and peripheral nerve blocks are used in only a minority of procedures. Trend analyses show that peripheral nerve blocks are gaining in popularity, whereas use of neuraxial anaesthetics is remaining relatively unchanged or even declining over time. Finally, significant disparities and variability in anaesthetic care seem to exist based on demographic and health-care-related factors. With anaesthesia playing an increasingly important part in population-based health-care delivery and evidence indicating improved outcome with use of regional anaesthesia, more research in this area is needed. Furthermore, prevalent disparities and variabilities in anaesthesia practice need to be specified further and addressed in the future.

Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion: a population-based study.

Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84,655 patients undergoing posterior lumbar fusion were identified and 7.28% (n = 6163) also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood product transfusion and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (odds ratio (OR) 1.50, confidence interval (CI) 1.38;1.62), blood product transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians.

Regional anesthesia in patients with significant comorbid disease.

An increasing body of evidence suggests that regional anesthesia does not only provide better pain control compared to systemic analgesic and anesthetic techniques but that it is associated with improved perioperative outcomes. As these benefits may be especially prominent in the patient population suffering from high comorbidity burden, anesthesiologists have to be familiar with associated factors that may complicate the decision to use regional anesthetics. This manuscript is intended to provide a brief overview of the recent literature regarding beneficial outcomes associated with the use of regional versus general anesthesia, before focusing on the discussion of the implications of specific comorbid states on the performance of regional anesthetic techniques.

National in-hospital morbidity and mortality trends after lumbar fusion surgery between 1998 and 2008.

Increasing numbers of posterior lumbar fusions are being performed. The purpose of this study was to identify trends in demographics, mortality and major complications in patients undergoing primary posterior lumbar fusion. We accessed data collected for the Nationwide Inpatient Sample for each year between 1998 and 2008 and analysed trends in the number of lumbar fusions, mean patient age, comorbidity burden, length of hospital stay, discharge status, major peri-operative complications and mortality. An estimated 1 288 496 primary posterior lumbar fusion operations were performed between 1998 and 2008 in the United States. The total number of procedures, mean patient age and comorbidity burden increased over time. Hospital length of stay decreased, although the in-hospital mortality (adjusted and unadjusted for changes in length of hospital stay) remained stable. However, a significant increase was observed in peri-operative septic, pulmonary and cardiac complications. Although in-hospital mortality rates did not change over time in the setting of increases in mean patient age and comorbidity burden, some major peri-operative complications increased. These trends highlight the need for appropriate peri-operative services to optimise outcomes in an increasingly morbid and older population of patients undergoing lumbar fusion.

Meta-analysis of cause of death following total joint replacement using different thromboprophylaxis regimens.

We performed a meta-analysis of modern total joint replacement (TJR) to determine the post-operative mortality and the cause of death using different thromboprophylactic regimens as follows: 1) no routine chemothromboprophylaxis (NRC); 2) Potent anticoagulation (PA) (unfractionated or low-molecular-weight heparin, ximelagatran, fondaparinux or rivaroxaban); 3) Potent anticoagulation combined (PAC) with regional anaesthesia and/or pneumatic compression devices (PCDs); 4) Warfarin (W); 5) Warfarin combined (WAC) with regional anaesthesia and/or PCD; and 6) Multimodal (MM) prophylaxis, including regional anaesthesia, PCDs and aspirin in low-risk patients. Cause of death was classified as autopsy proven, clinically certain or unknown. Deaths were grouped into cardiopulmonary excluding pulmonary embolism (PE), PE, bleeding-related, gastrointestinal, central nervous system, and others (miscellaneous). Meta-analysis based on fixed effects or random effects models was used for pooling incidence data. In all, 70 studies were included (99 441 patients; 373 deaths). The mortality was lowest in the MM (0.2%) and WC (0.2%) groups. The most frequent cause of death was cardiopulmonary (47.9%), followed by PE (25.4%) and bleeding (8.9%). The proportion of deaths due to PE was not significantly affected by the thromboprophylaxis regimen (PA, 35.5%; PAC, 28%; MM, 23.2%; and NRC, 16.3%). Fatal bleeding was higher in groups relying on the use of anticoagulation (W, 33.8%; PA, 9.4%; PAC, 10.8%) but the differences were not statistically significant. Our study demonstrated that the routine use of PA does not reduce the overall mortality or the proportion of deaths due to PE.

Meningitis or epidural abscesses after neuraxial block for removal of infected hip or knee prostheses.

BACKGROUND: Infection, whether localized or systemic, can be a relative contraindication to neuraxial anaesthesia. Data correlating neuraxial anaesthesia and the development of meningitis or epidural abscess in this setting are limited. METHODS: Retrospective chart review was performed on 710 medical records of patients admitted between 1998 and 2009 for removal of potentially infected total hip and total knee prostheses. Ultimately, 474 patients were identified as being infected. Factors that predisposed a patient to an immunocompromised state, and signs and symptoms of infection in the pre-, intra-, and postoperative stages were documented. Bacteraemic patients were reviewed for signs of neuraxial infection. The endpoint of follow-up was development of complications before hospital discharge. RESULTS: All 474 patients had removal of the infected prosthesis under neuraxial anaesthesia. Mean patient age was 65.5 yr (58% >65 yr) and mean length of hospital stay was 21 days. Patient characteristics included concurrent disease (65%), steroid use (5.3%), preoperative antibiotic use (50.8%), signs of inflammatory process (84%), bacteraemia (4.2%), and documented positive intraoperative joint cultures (88%). Using clinical standards for diagnosis of central neuraxial infection, patients developed infectious complications (incidence of 0.6% on 95% confidence interval), although three patients had findings attributable to anaesthesia, including epidural haematoma, psoas abscess, and back pain. CONCLUSIONS: Based on clinical criteria, our findings suggest that the incidence of central nervous system infection after neuraxial anaesthesia in patients with infected hip and knee prostheses is low after neuraxial block.

Cure of metastatic human colonic cancer in mice with radiolabeled monoclonal antibody fragments.

There is currently no method to cure patients with disseminated colorectal cancer, which is the third leading cancer killer in the Western World. This report shows that the GW-39 intrapulmonary micrometastatic human colonic cancer model in nude mice can be cured with radiolabeled antibodies against carcinoembryonic antigen, and that this approach of radioimmunotherapy is superior to conventional chemotherapy with 5-fluorouracil and leucovorin (5-FU/LV). Monovalent Fab fragments labeled with 131I are superior to intact IgG when survival was evaluated 3, 7, and 14 days after implantation, leading to cures in up to 90% of the mice. Histological results provide support for the differences in therapeutic efficacy observed. Microautoradiography was used to evaluate the intratumoral distribution of each form of antibody. The enhanced tumor control by Fab compared with IgG could be explained in part by the homogeneity of radioantibody distribution of Fab. Biodistribution analysis and initial dose rate calculations for all three forms of antibody also help explain the ability of 131I-labeled Fab to provide better tumor growth control than seen with 131I-labeled IgG. Thus, radioimmunotherapy may be a new modality to treat metastatic disease, particularly when using small antibody fragments.

Radioimmunotherapy of colorectal cancer in small volume disease and in an adjuvant setting: preclinical evaluation in comparison to equitoxic chemotherapy and initial results of an ongoing phase-I/II clinical trial.

The 5-year survival of colorectal cancer patients with distant metastases is below 30%, despite the development and use of a variety of chemotherapeutic regimens. Therefore, new therapeutic strategies are warranted. Whereas radioimmunotherapy (RIT) has shown disappointing results in bulky disease, it may be a promising therapeutic alternative in limited and small volume disease. The aim of this study was, therefore, to compare, in a preclinical study, the therapeutic efficacy of RIT in colorectal cancer to equitoxic chemotherapy, as well as to evaluate, in a pilot clinical trial, its efficacy in small volume disease. Nude mice, bearing subcutaneous or metastatic human colon cancer xenografts, were injected either with the unlabeled or 131I-labeled monoclonal antibodies (MAbs), CO17-1A (which is a murine IgG2a directed against a 41-kD membrane glycoprotein) or F023C5 (which is an anti-CEA MAb of murine IgG1 subtype), or were administered 5-fluorouracil/folinic acid (5-FU/LV) at equitoxic doses. In a pilot clinical study, 10 colorectal cancer patients with small volume metastatic disease (all lesions < or = 3 cm) have been entered so far in an ongoing mCi/m2-based dose escalation study with the 131I-labeled F023C5. In the animals, the maximum tolerated activities (MTD) of 131I-labeled CO17-1A and F023C5 were 300 microCi and 600 microCi, respectively, corresponding to blood doses of approximately 15 Gy each. Accordingly, myelotoxicity was dose-limiting. The MTD in the chemotherapy group was 0.6 mg 5-FU/1.8 mg LV, given as intravenous bolus 1 h apart for 5 subsequent days. Whereas no significant therapeutic effects were seen with both unlabeled MAbs or 5-FU/LV chemotherapy, tumor growth was retarded significantly with both radiolabeled antibodies. In the metastatic model, chemotherapy prolonged life for only a few weeks, whereas RIT led to cures in 35-55% of the animals. As was the case in the animals, myelotoxicity seems to be dose-limiting in patients as well. Encouraging anti-tumor effects were observed, lasting for up to more than 12 months. These data suggest that radioimmunotherapy may be a viable therapeutic option in colorectal cancer patients with limited disease. Myelotoxicity is the only dose-limiting organ toxicity. Although most patients were treated below the MTD, anti-tumor effects are encouraging. Further studies are ongoing.

Experimental studies on the role of antibody fragments in cancer radio-immunotherapy: Influence of radiation dose and dose rate on toxicity and anti-tumor efficacy.

Whereas bivalent fragments have been widely used for radio-immunotherapy, no systematic study has been published on the therapeutic performance of monovalent conjugates in vivo. The aim of our study was, therefore, to determine the therapeutic performance of (131)I-labeled Fab as compared to bivalent conjugates and to analyze factors that influence dose-limiting organ toxicity and anti-tumor efficacy. The maximum tolerated doses (MTDs) and dose-limiting organ toxicities of the (131)I-labeled anti-CEA antibody MN-14 [IgG, F(ab')2 and Fab] were determined in nude mice bearing s.c. human colon cancer xenografts. Mice were treated with or without bone marrow transplantation (BMT) or inhibition of the renal accretion of antibody fragments by D-lysine or combinations thereof. Toxicity and tumor growth were monitored. Radiation dosimetry was calculated from biodistribution data. With all 3 (131)I-labeled immunoconjugates [IgG, F(ab')2 and Fab], the red marrow was the only dose-limiting organ; MTDs were 260 microCi for IgG, 1,200 microCi for F(ab')2 and 3 mCi for Fab, corresponding to blood doses of 17 Gy, 9 Gy and 4 Gy, respectively. However, initial dose rates were 10 times higher with Fab as compared to IgG and 3 times higher as compared to F(ab')2. The MTD of all 3 immunoconjugates was increased by BMT by approximately 30%. In accordance with renal doses below 10 Gy, no signs of nephrotoxicity were observed. Despite lower absorbed tumor doses, at equitoxic dosing, Fab fragments were more effective at controlling tumor growth than the respective bivalent fragment or IgG, probably due to higher intratumoral dose rates. Our data indicate that the improved anti-tumor effectiveness of antibody fragments as compared to IgG and the higher myelotoxicity at comparably lower red marrow doses are most likely due to the higher initial dose rates observed with antibody fragments.

Therapeutic efficacy and dose-limiting toxicity of Auger-electron vs. beta emitters in radioimmunotherapy with internalizing antibodies: evaluation of 125I- vs. 131I-labeled CO17-1A in a human colorectal cancer model.

Recent clinical results suggest that higher anti-tumor efficacy may be achieved with internalizing monoclonal antibodies (MAbs) at lower toxicity when labeled with Auger-electron, as compared to conventional beta-emitters. The aim of our study was to compare the toxicity and anti-tumor efficacy of the 125I-labeled internalizing MAb, CO17-1A, with its 131I-labeled form in a human colon cancer model in nude mice. Biodistribution studies were performed in nude mice bearing s.c. human colon cancer xenografts. For therapy, the mice were injected either with unlabeled 125I- or 131I-labeled C017-1A at equitoxic doses. Control groups were left untreated, were given a radiolabeled isotype-matched irrelevant antibody or a tumor-specific, but noninternalizing antibody. The maximum tolerated activities (MTD) of 131I-and 125I-CO17-1A without artificial support were 300 microCi and 3 mCi, respectively. Myelotoxicity was dose-limiting; bone marrow transplantation allowed for an increase of the MTD to 400 microCi of 131I-17-1A, whereas the MTD of 125I-17-1A with bone marrow support had not been reached at 5 mCi. Whereas no significant therapeutic effects were seen with unlabeled C017-1A, tumor growth was retarded with 131I-CO17-1A. With the 125I-label, however, therapeutic results were clearly superior. In contrast, no significant difference was observed in the therapeutic efficacy of the 131I- vs. 125I-labeled, noninternalizing antibodies. Our data indicate a superiority of Auger-electron emitters, such as 125I, as compared to therapy with conventional beta-emitters with internalizing antibodies. The lower toxicity of Auger emitters may be due to the short path length of their low-energy electrons, which can reach the nuclear DNA only if the antibody is internalized (as is the case in antigen-expressing tumor tissue, but not in the stem cells of the red marrow).