Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New: Background: Recently, several retrospective studies have suggested that pulmonary complication is related with driving pressure more than any other ventilatory parameter. Thus, the authors compared driving pressure–guided ventilation with conventional protective ventilation in thoracic surgery, where lung protection is of the utmost importance. The authors hypothesized that driving pressure–guided ventilation decreases postoperative pulmonary complications more than conventional protective ventilation. Methods: In this double-blind, randomized, controlled study, 292 patients scheduled for elective thoracic surgery were included in the analysis. The protective ventilation group (n = 147) received conventional protective ventilation during one-lung ventilation: tidal volume 6 ml/kg of ideal body weight, positive end-expiratory pressure (PEEP) 5 cm H₂O, and recruitment maneuver. The driving pressure group (n = 145) received the same tidal volume and recruitment, but with individualized PEEP which produces the lowest driving pressure (plateau pressure–PEEP) during one-lung ventilation. The primary outcome was postoperative pulmonary complications based on the Melbourne Group Scale (at least 4) until postoperative day 3. Results: Melbourne Group Scale of at least 4 occurred in 8 of 145 patients (5.5%) in the driving pressure group, as compared with 18 of 147 (12.2%) in the protective ventilation group (P = 0.047, odds ratio 0.42; 95% CI, 0.18 to 0.99). The number of patients who developed pneumonia or acute respiratory distress syndrome was less in the driving pressure group than in the protective ventilation group (10/145 [6.9%] vs. 22/147 [15.0%], P = 0.028, odds ratio 0.42; 95% CI, 0.19 to 0.92). Conclusions: Application of driving pressure–guided ventilation during one-lung ventilation was associated with a lower incidence of postoperative pulmonary complications compared with conventional protective ventilation in thoracic surgery.

This study was performed to assess whether intubation is more difficult in obese patients and to assess the ability of a new index: the ratio of the neck circumference to thyromental distance (NC/TM), to predict difficult intubation in obese patients. The incidence of difficult tracheal intubation in 123 obese (BMI≥27.5 kg m⁻²) and 125 non-obese patients was compared. Difficult intubation was determined using the intubation difficulty scale (IDS≥5). The NC/TM ratio was calculated and its ability to predict difficult intubation in obese patients was compared with that of established predictors including high BMI, the Mallampati score, the Wilson score, NC, width of mouth opening, sternomental distance, TM, and a previous history of difficult intubation. Difficult intubation was more frequent in obese patients than in non-obese patients (13.8% vs 4.8%; P=0.016). Multivariate analysis revealed that the Mallampati score, the Wilson score, and NC/TM independently predicted difficult intubation in obese patients. Among these three indices, NC/TM showed the highest sensitivity and a negative predictive value, and largest area under the curve on an ROC curve. Difficult intubation was more common in obese patients and the NC/TM was a better method for predicting difficult intubation than other established indices.

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and ¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

Airway driving pressure, easily measured as plateau pressure minus PEEP, is a surrogate for alveolar stress and strain. However, the effect of its targeted reduction remains unclear. In this multicentre trial, patients undergoing lung resection surgery were randomised to either a driving pressure group (n=650) receiving an alveolar recruitment/individualised PEEP to deliver the lowest driving pressure or to a conventional protective ventilation group (n=650) with fixed PEEP of 5 cm H₂O. The primary outcome was a composite of pulmonary complications within 7 days postoperatively. The modified intention-to-treat analysis included 1170 patients (mean [standard deviation, sd]; age, 63 [10] yr; 47% female). The mean driving pressure was 7.1 cm H₂O in the driving pressure group vs 9.2 cm H₂O in the protective ventilation group (mean difference [95% confidence interval, CI]; -2.1 [-2.4 to -1.9] cm H₂O; P<0.001). The incidence of pulmonary complications was not different between the two groups: driving pressure group (233/576, 40.5%) vs protective ventilation group (254/594, 42.8%) (risk difference -2.3%; 95% CI, -8.0% to 3.3%; P=0.42). Intraoperatively, lung compliance (mean [sd], 42.7 [12.4] vs 33.5 [11.1] ml cm H₂O^-1; P<0.001) and Pa_o2 (median [inter-quartile range], 21.5 [14.5 to 30.4] vs 19.5 [13.5 to 29.1] kPa; P=0.03) were higher and the need for rescue ventilation was less frequent (6.8% vs 10.8%; P=0.02) in the driving pressure group. In lung resection surgery, a driving pressure-guided ventilation improved pulmonary mechanics intraoperatively, but did not reduce the incidence of postoperative pulmonary complications compared with a conventional protective ventilation. NCT04260451.

Fluid is restricted in thoracic surgery to reduce acute lung injury, and hydroxyethyl starches (HES) are often administered to reduce fluid amount. This strategy may contribute to the development of acute kidney injury (AKI). We evaluated the incidence, risk factors, and prognosis of AKI in thoracic surgery. We especially focused on whether fluid restriction/HES administration increased AKI. This is a retrospective study of patients undergoing thoracic surgery in a tertiary care academic center. Postoperative AKI was diagnosed within 72 hours after surgery based on the Acute Kidney Injury Network criteria. Demographic, intraoperative, and postoperative data were compared between non-AKI and AKI groups. Logistic regression was used to model the association between risk factors and AKI. Final analysis included 1442 patients. Of these, 74 patients developed AKI (5.1%). Crystalloid restriction (≤3 mL·kg·h) was unrelated to AKI, regardless of preoperative renal functions (odds ratio [OR], 0.5; 95% confidence interval [CI] 0.2-1.4). AKI occurred more often when HES were administered to the patients with decreased renal function (OR, 7.6; 95% CI, 1.5-58.1) or having >2 risk factors with normal renal function (OR, 7.2; 95% CI, 3.6-14.1). Multivariate analysis revealed several risk factors: angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, open thoracotomy, pneumonectomy/esophagectomy, diabetes mellitus, cerebrovascular disease, low albumin level, and decreased renal function. Fluid restriction neither increased nor was a risk factor for AKI. HES should be administered with caution in high-risk patients undergoing thoracic surgery.