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The fragility index (FI), the number of events the statistical significance a result depends on, and the number of patients lost to follow-up are important parameters for interpreting randomised clinical trial results. We evaluated these two parameters in randomised controlled trials in anaesthesiology. For this, we performed a systematic search of the medical literature, seeking articles reporting on anaesthesiology trials with a statistically significant difference in the primary outcome and published in the top five general medicine journals, or the top 15 anaesthesiology journals. We restricted the analysis to trials reporting clinically important primary outcome measures. The search identified 139 articles, 35 published in general medicine journals and 104 in anaesthesiology journals. The median (inter-quartile range) sample size was 150 (70-300) patients. The FI was 4 (2-17) and 3 (2-7), and the number of patients lost to follow-up was 0 (0-18) and 0 (0-6) patients in trials published in general medicine and anaesthesiology journals, respectively. The number of patients lost to follow-up exceeded the FI in 41 and 27% in trials in general medicine journals and anaesthesiology journals, respectively. The FI positively correlated with sample size and number of primary outcome events, and negatively correlated with the reported P-values. The results of this systematic review suggest that statistically significant differences in randomised controlled anaesthesiology trials are regularly fragile, implying that the primary outcome status of patients lost to follow-up could possibly have changed the reported effect.

Objective: To study the effect of postoperative complications (POC) on overall survival (OS) and disease-free survival (DFS) after surgical resection of colorectal liver metastases (CRLM). Summary Background Data: Morbidity rates after liver resection can reach 45%. The negative impact of POC on oncologic outcomes has been reported in various types of cancer, especially colorectal. However, data on the consequences of POC after CRLM resection on long-term survival are scarce. Methods: Eligible studies examining the association between POC after CRLM resection and OS/DFS were sought using the PubMed and Web of Science databases. A random-effects model was used to calculate pooled effect estimate for OS and DFS hazard ratios (HR), estimating between-study variance with restricted maximum likelihood estimator with Hartung–Knapp adjustment. Subgroup analysis was used to control the effect of POC on OS and DFS for: 1) Method used to define postoperative complications, 2) Exclusion of early postoperative death from survival analysis, 3) Method of data extraction used, and 4) Tumor and treatment characteristics. Results: Forty-one studies were deemed eligible, including 12,817 patients. POC patients had a significant risk of reduced OS compared with no POC group (HR 1.43 [95% CI: 1.3, 1.57], P < 0.0001). POC had also a negative impact on DFS. The HR for reduced DFS was 1.38 [95% CI 1.27, 1.49], P < 0.0001. The negative impact of POC on survival and recurrence was confirmed in subgroup analysis. Conclusions: Our findings evidence the negative impact of POC on survival and recurrence after CRLM resection.

Preclinical evidence has shown increased expression of mu opioid receptor 1 (MOR-1) in colorectal cancer although its association with disease-free and overall survival (DFS and OS) has not been investigated. We hypothesized that MOR-1 was overexpressed in tumor samples compared to normal tissue and this was associated with decreased DFS and OS. We carried out a retrospective study assessing the association of MOR-1 tumor expression with long-term outcomes by immunohistochemistry in normal and tumor samples from 174 colorectal cancer patients. The primary endpoint was five years of DFS. Secondary endpoints were five years of OS, the difference in MOR-1 expression between normal and tumor tissue and the occurrence of postoperative complications. Multivariable Cox regression showed no significant association between MOR-1 expression and DFS (HR 0.791, 95% CI 0.603–1.039, p = 0.092). MOR-1 expression was higher in tumor tissue compared to non-tumor tissue. No associations were found between MOR-1 expression and OS or postoperative complications. These findings suggest that although MOR-1 is over-expressed in colorectal cancer samples there is no association to increased risk of recurrence or mortality. Future studies are warranted to elucidate the role of cancer stage, genetic polymorphism, and quantitative assessment of MOR-1 over-expression on long-term outcomes in colorectal cancer.

Background and objectivesIn the context of opioid-sparing perioperative management, there is still little evidence from randomized controlled trials regarding the effectiveness of interfascial thoracic blocks. This study hypothesizes that receiving a serratus plane block reduces opioid requirements, pain scores, and rescue medication needs.MethodsThis double-blind, randomized controlled study was conducted on 60 adult females undergoing oncologic breast surgery. After general anesthesia, patients were randomly allocated to either conventional analgesia (control group, n=30) or single-injection serratus block with L-bupivacaine 0.25% 30mL (study group, n=30). First 24-hour total morphine consumption (primary outcome), pain scores at 1, 3, 6, 12, and 24 hours, time-to-first opioid rescue analgesia, and adverse effects were recorded.ResultsMedian 24 hours’ opioid dose was greater in the control group (median difference 9 mg (95% CI 4 to 14.5 mg); p<0.001). Proportional odds model showed that the study group has a lower probability of receiving opioid drugs (OR=0.26 (95% CI 0.10 to 0.68); p<0.001), while mastectomies have a higher probability of receiving them (OR=4.11 (95% CI 1.25 to 13.58); p=0.002). Pain scores in the study group were significantly lower throughout the follow-up period (p<0.001). Control group subjects needed earlier morphine rescue and had a higher risk of rescue dose requirement (p=0.002).ConclusionsInterfascial serratus plane block reduces opioid requirements and is associated with better pain scores and lower and later rescue analgesia needs in the first 24 hours, compared with conventional intravenous analgesia, in breast surgery.Trial registration numberNCT02905149.

Background Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumoperitoneum-related rises in driving pressure. Methods Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. “Targeted PEEP” (2 cm H2O above intraabdominal pressure) was compared with “standard PEEP” (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure. Results Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P &lt; 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels. Conclusions Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BACKGROUND: Tracheal intubation failure in patients with difficult airway is still not uncommon. While videolaryngoscopes such as the Glidescope offer better glottic vision due to an acute-angled blade, this advantage does not always lead to an increased success rate because successful insertion of the tube through the vocal cords may be the limiting factor. We hypothesize that combined use of Glidescope and fiberscope used only as a dynamic guide facilitates tracheal intubation compared to a conventional Glidescope technique with a preshaped nondynamic stylet. METHODS: One hundred sixty adult patients with predicted difficult airway were randomly assigned to a conventional Glidescope (standard Glidescope group) or a combined Glidescope + fiberscope group intubation. In the Glidescope + fiberscope group under direct vision from the Glidescope, tracheal intubation was performed using the fiberscope as a guide without using fiberoptic vision, while in the standard Glidescope group, a conventional stylet-guided intubation technique was performed. We evaluated the rate of tracheal intubation success at first attempt as the primary end point (Fisher exact test). The difference between groups in airway injury, time to successful intubation, and the need for an alternative technique was also evaluated. RESULTS: First-attempt intubation success was higher in the Glidescope + fiberscope group than in the standard Glidescope group (91% vs 67%; P = .0012; fragility index, 8; absolute risk reduction, 24% [95% CI, 12%–36%]). Median time to successful tracheal intubation was shorter in the Glidescope + fiberscope group (50 vs 64 seconds; P = .035). Airway injury rate was lower in the Glidescope + fiberscope group than in the standard Glidescope group (1% vs 11%; P = .035; fragility index, 1; absolute risk reduction, 10% [95% CI, 3%–18%]). Alternative rescue technique requirements to achieve tracheal intubation were higher in the standard Glidescope group (24% vs 4%; P < .001; fragility index, 7). CONCLUSIONS: The use of a dynamic, flexible guide during a Glidescope laryngoscopy in patients with a predicted difficult airway compared to a standard intubation technique improves first-attempt intubation success, decreases the incidence of airway injury and time to successful intubation, as well as the need of an alternative technique to succeed.