Frendl, György

Abstract Rationale Postoperative pulmonary complications (PPCs) importantly contribute to postoperative morbidity and mortality, particularly for American Society of Anesthesiologists (ASA) physical status III patients. It remains unclear whether risk factors for PPCs depend on sex. We hypothesised that sex modifies the relationship between perioperative risk factors and PPCs in ASA III patients undergoing noncardiothoracic surgery with general anesthesia. Methods We performed a secondary analysis of prospective data from 1,202 ASA III patients undergoing non-cardiothoracic surgery. Data consisted of preoperative demographics, comorbidities, intraoperative physiology, medications, and procedure information. The primary outcome was a composite of PPCs by postoperative day 7. Mixed-effects linear models incorporated sex as main effect and interaction with covariates. Results Age, chronic obstructive pulmonary disease, upper abdominal surgery, surgical duration, and emergency surgery significantly increased the odds of ≥ 1 PPC by postoperative day 7. Male patients presented a higher rate of ≥ 3 PPCs, and mechanical ventilation was less protective in female patients. Yet, sex did not significantly modify the relationship between perioperative factors and the primary outcome (no p<0.05 for the interaction effect with sex). In the secondary analysis, gastroesophageal reflux disease affected atelectasis more strongly in male than female patients (relative odds-ratios for female versus male =0.27; 95% CI 0.13 to 0.57). Conclusions In ASA III patients undergoing non-cardiothoracic surgery with general anesthesia, perioperative factors are predominantly not significantly modified by sex in their relationship to PPCs. GERD’s association with atelectasis in male patients could be explored in future prospective studies as a target for reducing pulmonary complications. This abstract is funded by: NHLBI - UH3 HL140177

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. Setting: ICUs. Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo ( n = 45 and n = 60, respectively). Interventions: IV angiotensin II or placebo. Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo ( p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo ( p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo ( p = 0.001), respectively. Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Abstract Rationale Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. Objectives To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. Methods The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Measurements and Main Results Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159–1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg. Conclusions NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).

Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO 2 /FiO 2 ) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO 2 /FiO 2 measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO 2 /FiO 2 . The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO 2 /FiO 2 values. Median SpO 2 /FiO 2 in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO 2 /FiO 2 and ARDS ( P ≤ .001). The SpO 2 /FiO 2 was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO 2 /FiO 2 < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO 2 /FiO 2 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO 2 /FiO 2 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO 2 /FiO 2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. Conclusions: The SpO 2 /FiO 2 , measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.

Abstract Rationale Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies. Objectives To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS). Methods In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions. Measurements and Main Results Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1–4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78–0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9–5.7). Conclusions ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).