The relationship between study findings and publication outcome in anesthesia research following implementation of mandatory trial registration: A systematic review of publication bias.

Previously, we reviewed 1052 randomized-controlled trial abstracts presented at the American Society of Anesthesiologists annual meetings from 2001-2004. We found significant positive publication bias in the period examined, with the odds ratio for abstracts with positive results proceeding to journal publication over those with null results being 2.01 [95% confidence interval: 1.52, 2.66; P < 0.001]. Mandatory trial registration was introduced in 2005 as a required standard for publication. We sought to examine whether mandatory trial registration has decreased publication bias in the anesthesia and perioperative medicine literature. We reviewed all abstracts from the 2010-2016 American Society of Anesthesiologists meetings that reported on randomized-controlled trials in humans. We scored the result of each abstract as positive or null according to a priori definitions. We systematically searched for any subsequent publication of the studies and calculated the odds ratio for journal publication, comparing positive vs null studies. We compared the odds ratio from the 2010-2016 abstracts (post-mandatory trial registration) with the odds ratio from the 2001-2004 abstracts (pre-mandatory trial registration) as a ratio of odds ratios. We defined a 33% decrease in the odds ratio as significant, corresponding to a new odds ratio of 1.33. We reviewed 9789 abstracts; 1049 met inclusion criteria as randomized-controlled trials, with 542 (51.7%) of the abstracts going on to publication. The odds ratio for abstracts with positive results proceeding to journal publication was 1.28 [95% CI: 0.97, 1.67; P = 0.076]. With adjustment for sample size and abstract quality, the difference in publication rate between positive and null abstracts was statistically significant (odds ratio 1.34; 95% CI: 1.02, 1.76; P = 0.037). The ratio of odds ratios, comparing the odds ratio from the 2010-2016 abstracts (post-mandatory trial registration) to the odds ratio from the 2001-2004 abstracts (pre-mandatory trial registration), was 0.63 (95% CI: 0.43, 0.93); P = 0.021). We present the first study in the anesthesia and perioperative medicine literature that examines and compares publication bias over two discrete periods of time, prior to and after the implementation of mandatory trial registration. Our results suggest that the amount of publication bias has decreased markedly following implementation of mandatory trial registration. However, some positive publication bias in the anesthesia and perioperative medicine literature remains.

Trial registration of abstracts from the American Society of Anesthesiologists Meetings 2010-2016: A review of prospective trial registration and selective outcome reporting.

Mandatory prospective trial registration was introduced in 2005 to reduce publication bias and selective outcome reporting. In this study, we measured the proportion of prospective trial registration in randomized controlled trials in the anesthesia literature after this introduction, discrepancies between these trial protocols and subsequent publications, the association between being prospectively registered and reporting positive or negative results, and between being prospectively registered and achieving publication. We reviewed all abstracts from the American Society of Anesthesiologists annual meetings between 2010-2016 and included randomized controlled trials in humans. The abstract conclusions were scored as positive or negative according to predetermined definitions. We conducted a systematic search for trial registration and subsequent publication. Of the 9789 abstracts reviewed, 1070 abstracts were included. 222 (21%) of these abstracts had undergone prospective trial registration. 168/222 (76%) had a corresponding journal publication. 81(48%) had a major discrepancy between registration and publication. 149 (67%) of the abstracts with registration had positive outcomes compared with 616 (73%) of those without (Odds Ratio 0.77; 95% CI: 0.56 to 1.06; P = 0.105). Abstracts that had been registered were more likely to proceed to publication than those that had not (Odds Ratio 3.82; 95% CI 2.73 to 5.35; P < 0.001). The proportion of randomized controlled trials being prospectively registered in anesthesia remains low. Discrepancies between registry entries and corresponding journal publications are common. There was no association between prospective trial registration and subsequent positive outcomes. There was a strong association between prospective trial registration and the likelihood of progression to journal publication.

Reported definitions of intraoperative hypotension in adults undergoing non-cardiac surgery under general anaesthesia: a review.

BACKGROUND: Intraoperative hypotension (IOH) during non-cardiac surgery is common and associated with major adverse kidney, neurological and cardiac events and even death. Given that IOH is a modifiable risk factor for the mitigation of postoperative complications, it is imperative to generate a precise definition for IOH to facilitate strategies for avoiding or treating its occurrence. Moreover, a universal and consensus definition of IOH may also facilitate the application of novel and emerging therapeutic interventions in treating IOH. We conducted a review to systematically record the reported definitions of intraoperative hypotension in adults undergoing non-cardiac surgery under general anaesthesia. METHODS: In accordance with Cochrane guidelines, we searched three online databases (OVID [Medline], Embase and Cochrane Library) for all studies published from 1 January 2000 to 6 September 2020. We evaluated the number of studies that reported the absolute or relative threshold values for defining blood pressure. Secondary aims included evaluation of the threshold values for defining IOH, the methodology for accounting for the severity of hypotension, whether the type of surgical procedure influenced the definition of IOH, and whether a study whose definition of IOH aligned with the Perioperative Quality Initiative-3 workgroup (POQI) consensus statement for defining was more likely to be associated with determining an adverse postoperative outcome. RESULTS: A total of 318 studies were included in the final qualitative synthesis. Most studies (n = 249; 78.3%) used an absolute threshold to define hypotension; 150 (60.5%) reported SBP, 117 (47.2%) reported MAP, and 12 (4.8%) reported diastolic blood pressure (DBP). 126 (39.6%) used a relative threshold to define hypotension. Of the included studies, 153 (48.1%) did not include any duration variable in their definition of hypotension. Among the selected 318 studies 148 (46.5%) studies defined IOH according to the POQI statement. When studies used a "relative blood pressure change" to define IOH, there was a weaker association in detecting adverse postoperative outcomes compared to studies who reported "absolute blood pressure change" (χ2(2) = 10.508, P = 0.005, Cramér's V = 0.182). When studies used the POQI statement definition of hypotension or defined IOH by values higher than the POQI statement definition there were statistical differences observed between IOH and adverse postoperative outcomes (χ2(1) = 6.581, P = 0.037, Cramér's V = 0.144). When both the duration of IOH or the numbers of hypotensive epochs were evaluated, we observed a significantly stronger relationship between the definition of IOH use the development of adverse postoperative outcomes. (χ2(1) = 4.860, P = 0.027, Cramér's V = 0.124). CONCLUSIONS: Most studies defined IOH by absolute or relative changes from baseline values. There are substantial inconsistencies in how IOH was reported. Further, definitions differed across different surgical specialities. Our findings further suggest that IOH should be defined using the absolute values stated in the POQI statement i.e., MAP < 60-70 mmHg or SBP < 100 mmHg. Finally, the number of hypotensive epochs or time-weighted duration of IOH should also be reported.

MEasuring the impact of Anesthetist-administered medications volumeS on intraoperative flUid balance duRing prolonged abdominal surgEry (MEASURE Study).

BACKGROUND: The contribution of intraoperative anesthetist-administered medications (IAAMs) to the total volume of intraoperative intravenous (IV) fluid therapy and their association with postoperative outcomes has never been formally investigated. METHODS: We performed a retrospective study of adult patients undergoing pancreaticoduodenectomy. The volume of IAAMs, crystalloids and colloids, blood and blood products, blood loss, urine output and intraoperative fluid balance were collected. The contribution of IAAMs to the total intraoperative IV fluid volume and postoperative complications was evaluated. RESULTS: A total of 152 consecutive patients were included. The median volume of IAAMs was 363.8 mL (interquartile range [IQR], (241.0-492.5) delivered at a median rate of 0.61 mL kg hr-1 (0.40-0.87) over a median duration of surgery of 489 minutes (416.3-605.3). This increased the total administered fluid volume by 5.2% (95% confidence intervals [CI]: 4.6, 5.9%) (Cohen's d=1.33, P<0.001). The volume of IAAMs was comparable to the intraoperative colloid volume administered (median colloid volume, 400 mL). Overall, fluid volumes correlated significantly with the severity of complications (P=0.011), and the correlation strength increased when the IAAMs volume was included (P=0.005). On addition of IAAMs, the area under the receiver operator characteristic curve for prediction of postoperative complications increased from 0.580 (95%CI: 0.458, 0.701) to 0.603 (95%CI: 0.483, 0.723), P=0.041). CONCLUSIONS: IAAMs significantly increased the total administered fluid volume during pancreaticoduodenectomy. Their inclusion increases the accuracy of postoperative complications predictions. These findings support their inclusion in fluid volumes and balances in future interventional studies.

Rapid response team activation after major hip surgery: A case series.

INTRODUCTION: We describe the demographic, preoperative, surgical, anesthetic, and postoperative characteristics of patients who required a rapid response team (RRT) activation after major hip surgery. We determined the characteristics and outcomes of patients that require RRTs after major hip surgery, and their associations with mortality. PRESENTATION OF CASES: We retrospectively reviewed adult patients undergoing major hip surgery in a university teaching hospital. We included patients who had an RRT or "code blue" activation post-surgery and within the index hospital admission. We extracted patient, surgical, anesthetic, and postoperative variables. We explored differences between patients who survived their index hospital stay and those who died. DISCUSSION: 187 (9%) patients had a postoperative RRT activation. The median age was 84.0 (78-90) years; 125 (67%) were female, and most patients had significant comorbidities. The median Charlson Comorbidity Index (CCI) was 5.0 (4.0-7.0). Patients were frail (68%), ASA physical status ≥Class 3 (91%) and underwent emergency surgery (88%). Death after RRT activation occurred in 1 in 7 patients. Compared to patients who survived RRT activation, those who died had a higher mean CCI (6.5 [1.8] vs. 5.5 [2.1], P = 0.02), were more frail (80.1% vs. 56.5%, OR = 3.2, 95% CI: 1.2,8.1; P = 0.03), and received less intraoperative opioids (intravenous morphine equi-analgesia: median = 5.8 (0.1-8.20 vs. 11.7 (3.7-19.0) mg, P = 0.03). CONCLUSION: Mortality after RRT activation is associated with non-modifiable patients factors rather than surgical or anesthesia factors. Our findings provide opportunities for the implementation of strategies aimed at improving postoperative outcomes.

Financial burden of postoperative complications following colonic resection: A systematic review.

BACKGROUND: Colonic resection is a common surgical procedure that is associated with a high rate of postoperative complications. Postoperative complications are expected to be major contributors to hospital costs. Therefore, this systematic review aims to outline the health costs of postoperative complications following colon resection surgery. METHODS: MEDLINE, Excerpta Medica database, Cochrane, and Economics literature medical databases were searched from 2010 to 2019 to identify English studies containing an economic evaluation of postoperative complications following colonic resection in adult patients. All surgical techniques and indications for colon resection were included. Eligible study designs included randomized trials, comparative observational studies, and conference abstracts. RESULTS: Thirty-four articles met the eligibility criteria. We found a high overall complication incidence with associated increased costs ranging from $2290 to $43,146. Surgical site infections and anastomotic leak were shown to be associated with greater resource utilization relative to other postoperative complications. Postoperative complications were associated with greater incidence of hospital readmission, which in turn is highlighted as a significant financial burden. Weak evidence demonstrates increased complication incidence and costlier complications with open colon surgery as compared to laparoscopic surgery. Notably, we identified a vast degree of heterogeneity in study design, complication reporting and costing methodology preventing quantitative analysis of cost results. CONCLUSIONS: Postoperative complications in colonic resection appear to be associated with a significant financial burden. Therefore, large, prospective, cost-benefit clinical trials investigating preventative strategies, with detailed and consistent methodology and reporting standards, are required to improve patient outcomes and the cost-effectiveness of our health care systems.

Postoperative complications and hospital costs following small bowel resection surgery.

BACKGROUND: Postoperative complications after major gastrointestinal surgery are a major contributor to hospital costs. Thus, reducing postoperative complications is a key target for cost-containment strategies. We aimed to evaluate the relationship between postoperative complications and hospital costs following small bowel resection. METHODS: Postoperative complications were recorded for 284 adult patients undergoing major small bowel resection surgery between January 2013 and June 2018. Complications were defined and graded according to the Clavien-Dindo classification system. In-hospital cost of index admission was calculated using an activity-based costing methodology; it was reported in US dollars at 2019 rates. Regression modeling was used to investigate the relationships among a priori selected perioperative variables, complications, and costs. FINDINGS: The overall complication prevalence was 81.6% (95% CI: 85.7-77.5). Most complications (69%) were minor, but 22.9% of patients developed a severe complication (Clavien-Dindo grades III or IV). The unadjusted median total hospital cost for patients with any complication was 70% higher than patients without complications (median [IQR] USD 19,659.64 [13,545.81-35,407.14] vs. 11,551.88 [8,849.46-15,329.87], P < 0.001). The development of 1, 2, 3, and ≥ 4 complications increased hospital costs by 11%, 41%, 50%, and 195%, respectively. Similarly, more severe complications incurred higher hospital costs (P < 0.001). After adjustments were made (for the Charlson Comorbidity Index, anemia, surgical urgency and technique, intraoperative fluid administration, blood transfusion, and hospital readmissions), a greater number and increased severity of complications were associated with a higher adjusted median hospital cost. Patients who experienced complications had an adjusted additional median cost of USD 4,187.10 (95% CI: 1,264.89-7,109.31, P = 0.005) compared to those without complications. CONCLUSIONS: Postoperative complications are a key target for cost-containment strategies. Our findings demonstrate a high prevalence of postoperative complications following small bowel resection surgery and quantify their associated increase in hospital costs. TRIAL REGISTRATION: Australian Clinical Trials Registration number: 12620000322932.

The financial burden of complications following rectal resection: A cohort study.

To investigate the costs associated with postoperative complications following rectal resection.Rectal resection is a major surgical procedure that carries a significant risk of complications. The occurrence of complications following surgery has both health and financial consequences. There are very few studies that examine the incidence and severity of complications and their financial implications following rectal resection.We identified 381 consecutive patients who underwent a rectal resection within a major university hospital. Patients were included using the International Classification of Diseases (ICD) codes. Complications in the postoperative period were reported using the validated Clavien-Dindo classification system. Both the number and severity of complications were recorded. Activity-based costing methodology was used to report financial outcomes. Preoperative results were also recorded and assessed.A 76.9% [95% CI: 68.3:86.2] of patients experienced one or more complications. Patients who had a complication had a median total cost of $22,567 [IQR 16,607:33,641]. Patients who did not have a complication had a median total cost of $15,882 [IQR 12,971:19,861]. The adjusted additional median cost for patients who had a complication was $5308 [95% CI: 2938:7678] (P < .001). Patients who experienced a complication tended to undergo an open procedure (P = .001), were emergent patients (P = .003), preoperatively had lower albumin levels (36 vs 38, P = .0003) and were anemic (P = .001).Complications following rectal resection are common and are associated with increased costs. Our study highlights the importance of evaluating and preventing complications in the postoperative period.

The hospital costs of complications following colonic resection surgery: A retrospective cohort study.

BACKGROUND: Colonic resection is a common surgical procedure associated with a high rate of postoperative complications. The aim of this observational study is to estimate the in-hospital costs of complications and to identify perioperative variables associated with complication development following colon resection surgery. MATERIALS AND METHODS: We conducted a single-centre cohort study with retrospective data collection of 487 patients undergoing colonic resection surgery between 2013 and 2018. Postoperative complications were graded according to the Clavien-Dindo classification system. In-hospital cost of index admission is reported in 2019 United States Dollars. Regression modelling was used to investigate the relationship of a priori selected perioperative variables and presence of complications and costs. RESULTS: Overall complication prevalence was 69.6% (95%CI:65.5%-73.7%). Median [interquartile range] cost of patients with postoperative complications was significantly increased as compared to patients without complications ($17,963 [13,533:25,178] vs $12,578 [10,196:16,140]; p < 0.0001). Clavien-Dindo Grade I, II, III and IV complications increased costs by 15.8%, 36.8%, 169.4% and 240.1% respectively (p < 0.0001). Presence of complications was significantly associated with Charlson Comorbidity Index (Odds ratio (OR) per 1-unit increase: 1.09; 95%CI:1.02 to 1.17), preoperative albumin levels (OR per 1-unit increase: 0.94; 95%CI:0.90 to 0.98) and open as compared to laparoscopic resection (OR: 2.41; 95%CI:1.32 to 4.42). CONCLUSIONS: There is a high prevalence of complications following colonic resection surgery. Postoperative complications, including minor complications (Clavien-Dindo Grade I-II), were associated with a significant increase in hospital costs and are a key target for cost containment strategies.

Health costs of post-operative complications following rectal resection: a systematic review.

BACKGROUND: Post-operative complications following rectal resection pose significant health and cost implications for patients and health providers. The objective of this study is to review the associated cost of complications following rectal resection. This included reporting on the proportion and severity of these complications, associated length of stay and surgical technique used. Studies were sourced from Embase OVID, MEDLINE OVID (ALL) and Cochrane Library databases by utilizing a search strategy. METHODS: This search contained studies from 1 January 2010 until 13 February 2019. Studies were included from the year 2010 to account for the implementation of enhanced recovery after surgery protocols. Studies that reported the financial cost associated with complications were included. Any indication for rectal resection was considered. Data was extracted into a formatted table and a narrative synthesis was performed. RESULTS: We identified 13 eligible studies for inclusion. There was strong evidence to suggest that complications are associated with increased costs. There was considerable variation as to the costs attributable to complications ($1443 (P < 0.001) to $17 831 (P < 0.0012), n = 12). The presence of complications was associated with an increased length of stay (5.54 (P-value not given) to 21.04 (P < 0.0001) days, n = 7). There was significant variation in the proportion of complications (6.41 to 64.71%, n = 8). Weak evidence existed around surgical technique used and the associated cost of complications. There was considerable heterogeneity among included studies. CONCLUSIONS: Complications following rectal resection increased health costs. Costs should be standardized and provide a clear methodology for their calculation. Complications should be standardized and include a grading of severity.

Intraoperative oxygen challenge for toleration of single lung ventilation in a patient with severe obstructive airway disease: A case report.

Perioperative risk assessment is complex in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery. A 70-year-old female with severe chronic obstructive pulmonary disease and previous right middle and lower lobectomy, presented for left lower lobe superior segmentectomy. Respiratory function tests revealed a forced expiratory volume in 1 second of 0.72L, a forced vital capacity of 1.93L, and a carbon monoxide transfer factor of 10.0 ml/min/mmHg. A cardiopulmonary exercise test demonstrated little ventilatory reserve with profound arterial desaturation on peak exercise, however, a normal peak oxygen consumption (16.7 ml/min/kg) and a nadir minute ventilation/carbon dioxide slope of 24 implied a limited risk of perioperative cardiovascular morbidity. Given these conflicting results we performed an intraoperative oxygen challenge test under general anaesthesia with sequential ventilation of different lobes of the lung. We demonstrate the use of the oxygen challenge test as an effective intervention to further assess safety and tolerance of anaesthesia of patients with limited respiratory reserve being assessed for further complex redo lung resection surgery. Further, this test was a risk stratification tool that allowed informed decisions to be made by the patient about therapeutic options for treating their lung cancer. The prognostic value of traditional physiological parameters in patients with chronic obstructive pulmonary disease who have undergone previous lung resection surgery is uncertain. The intraoperative oxygen challenge test is another risk stratification tool to assist clinicians in assessment of safety and tolerance of anaesthesia for patients being considered for lung resection.