Richard Hinds

Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial

IMPORTANCE Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear. OBJECTIVE To evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS. DESIGN, SETTING, AND PARTICIPANTS A multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 16 US academic hospitals. Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score ≥4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified intention-to-treat analysis cohort. INTERVENTIONS Administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death. MAIN OUTCOMES AND MEASURES The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A final α level of .0737 (α = .10 overall) was required for statistical significance of the primary outcome. RESULTS Among 390 analyzed patients (median age, 57 years; 187 [48%] women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively; odds ratio, 1.24 [92.6% CI, 0.67 to 2.31], P = .53). No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days (mean [90% CI] difference, -0.26 [-1.46 to 0.94] days; P = .72); ICU length of stay, mean (SD), 5.2 (7.0) days vs 5.4 (7.0) days (mean [90% CI] difference, -0.16 [-1.75 to 1.43] days; P = .87); hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days (mean [90% CI] difference, -0.27 [-1.96 to 1.42] days; P = .79); or 28-day survival, 90% vs 90% (hazard ratio [90% CI], 1.03 [0.60 to 1.79]; P = .92) or 1-year survival, 73% vs 75% (hazard ratio [90% CI], 1.06 [0.75 to 1.50]; P = .79). Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%; odds ratio [90% CI], 2.27 [0.92 to 5.61]; P = .13). RESULTS Among 390 analyzed patients (median age, 57 years; 187 [48%] women), median (IQR) hospital length of stay was 6 (3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (OR, 1.24; 92.6%CI, 0.67-2.31). No significant differences were seen in secondary outcomes or adverse events. [table: see text] CONCLUSIONS AND RELEVANCE Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01504867.

Lung Injury Prevention with Aspirin (LIPS-A): a protocol for a multicentre randomised clinical trial in medical patients at high risk of acute lung injury

Introduction Acute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI. Methods and analysis LIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy.

A video to improve patient and surrogate understanding of cardiopulmonary resuscitation choices in the ICU: a randomized controlled trial.

Objective:To determine if a video depicting cardiopulmonary resuscitation and resuscitation preference options would improve knowledge and decision making among patients and surrogates in the ICU. Design:Randomized, unblinded trial. Setting:Single medical ICU. Patients:Patients and surrogate decision makers in the ICU. Interventions:The usual care group received a standard pamphlet about cardiopulmonary resuscitation and cardiopulmonary resuscitation preference options plus routine code status discussions with clinicians. The video group received usual care plus an 8-minute video that depicted cardiopulmonary resuscitation, showed a simulated hospital code, and explained resuscitation preference options. Measurements and Main Results:One hundred three patients and surrogates were randomized to usual care. One hundred five patients and surrogates were randomized to video plus usual care. Median total knowledge scores (0–15 points possible for correct answers) in the video group were 13 compared with 10 in the usual care group, p value of less than 0.0001. Video group participants had higher rates of understanding the purpose of cardiopulmonary resuscitation and resuscitation options and terminology and could correctly name components of cardiopulmonary resuscitation. No statistically significant differences in documented resuscitation preferences following the interventions were found between the two groups, although the trial was underpowered to detect such differences. A majority of participants felt that the video was helpful in cardiopulmonary resuscitation decision making (98%) and would recommend the video to others (99%). Conclusions:A video depicting cardiopulmonary resuscitation and explaining resuscitation preference options was associated with improved knowledge of in-hospital cardiopulmonary resuscitation options and cardiopulmonary resuscitation terminology among patients and surrogate decision makers in the ICU, compared with receiving a pamphlet on cardiopulmonary resuscitation. Patients and surrogates found the video helpful in decision making and would recommend the video to others.

Monitoring of exhaled carbon monoxide to promote preoperative smoking abstinence.

OBJECTIVE Brief preoperative abstinence from cigarette smoking reduces risk for perioperative complications in surgical patients. This study tested the hypothesis that the efficacy of brief advice recommending abstinence the morning of surgery would be increased if patients were informed that exhaled carbon monoxide (CO) levels would be monitored to assess compliance. METHOD Cigarette smokers scheduled for elective surgery were randomized to 2 groups. Subjects in both groups received brief advice (BA) recommending smoking abstinence on the morning of surgery. The CO-informed + BA group was also told that their smoking status would be checked before surgery using exhaled CO monitoring; the other group (BA only) was not. RESULTS CO levels on the morning of surgery were not significantly different in the CO-informed + BA (n = 80) and BA-only groups (n = 84; M = 9.7, SD = 8.0, and M = 9.3, SD = 6.6 parts per million (ppm), respectively, p = .67). When the data from both groups were combined and compared with data from 506 additional surgical patients receiving only usual care, CO levels were significantly higher in those patients receiving usual care. CONCLUSIONS Informing patients that their smoking status would be checked the morning of surgery by CO monitoring does not further increase the efficacy of BA to abstain the morning of surgery.

Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome.

Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. Design: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%). Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.

Development, validation, and results of a survey to measure understanding of cardiopulmonary resuscitation choices among ICU patients and their surrogate decision makers

BackgroundShared-decision-making about resuscitation goals of care for intensive care unit (ICU) patients depends on a basic understanding of cardiopulmonary resuscitation (CPR). Our objective was to develop and validate a survey to assess comprehension of CPR among ICU patients and surrogate decision-makers.MethodsWe developed a 12-item verbally-administered survey incorporating input from patients, clinicians, and expert focus groups.ResultsWe administered the survey to 32 ICU patients and 37 surrogates, as well as to 20 resident physicians to test discriminative validity. Median (interquartile range) total knowledge scores were 7 (5-10) for patients, 9 (7-12) for surrogates, and 14.5 (14-15) for physicians (p <.001). Forty-four percent of patients and 24% of surrogates could not explain the purpose of CPR. Eighty-eight percent of patients and 73% of surrogates could not name chest compressions and breathing assistance as two components of CPR in the hospital. Forty-one percent of patients and 24% of surrogates could not name a single possible complication of CPR. Forty-three percent of participants could not specify that CPR would be performed with a full code order and 25% of participants could not specify that CPR would not be performed with a do-not-resuscitate order. Internal consistency (Cronbach’s alpha = 0.97) and test-retest reliability (Pearson correlation = 0.96, p < .001) were high.ConclusionsThis easily administered survey, developed to measure knowledge of CPR and resuscitation preference options among ICU patients and surrogates, showed strong face validity, content validity, internal consistency, test-retest reliability, and discriminative validity. A substantial proportion of ICU patients and surrogates decision-makers have poor knowledge of CPR and basic resuscitation options.

Reducing secondhand smoke exposure of children undergoing surgery.

OBJECTIVE To determine the attitudes and beliefs of both parents and surgical clinicians regarding interventions to reduce secondhand smoke (SHS) exposure in children undergoing surgery. METHODS Structured interviews were conducted with 25 parents of children scheduled for elective procedures and 10 surgical clinicians. RESULTS Major themes identified in parent interviews included: (1) parents are receptive to learning about the surgical risks posed by SHS exposure; (2) many are already attempting to reduce SHS exposure, and; (3) parents are more accepting of SHS mitigation procedure than a recommendation to quit smoking. Clinicians were receptive to addressing perioperative SHS exposure. CONCLUSIONS Both parents and clinicians are receptive to clinician-delivered interventions to reduce the SHS exposure of children scheduled for elective surgery.