Abstract Background Pneumonia is the most common ICU-acquired infection and source of potential sepsis in ICU populations but can be difficult to diagnose in real-time. Despite limited data, rapid initiation of antibiotics is endorsed by society guidelines. We hypothesized that a post-hoc analysis of a recent randomized pilot study would show no difference between two antibiotic initiation strategies. Methods The recent Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP) was a pragmatic cluster-randomized pilot of antibiotic initiation strategies for intubated patients with suspected but not yet proven ICU-acquired pneumonia. Participating ICUs were cluster-randomized to either an immediate initiation protocol or a specimen-initiated protocol where a gram stain was required for initiation of antibiotics. Patients in the study were divided into one of seven mutually exclusive outcome rankings (DOOR): 1) Survival, No Pneumonia, No adverse events; 2) Survival, Pneumonia, No adverse events; 3) Survival, No Pneumonia, ventilator-free-alive days ≤14; 4) Survival, Pneumonia, ventilator-free-alive days ≤14; 5) Survival, No Pneumonia, Subsequent episode of suspected pneumonia; 6) Survival, Pneumonia, Subsequent episode of suspected pneumonia; and 7) Death. These rankings were further refined using the duration of antibiotics prescribed for pneumonia (RADAR). Analysis was performed using R and adjusted for clustering. Results There were 186 patients enrolled in the study: 93 in each group. After applying the DOOR analysis, a randomly selected patient in the specimen-initiated group was just as likely to have a better outcome as a patient in the immediate initiation group (DOOR probability: 50.8%; 95% CI: 42.7-58.9%). After applying the RADAR analysis, the likelihood of a randomly selected patient in the specimen-initiated arm having a better outcome than a patient in the immediate arm was 52.5% (95% CI: 44.2-60.6%; p=0.31). Conclusion We found that patients in whom antibiotics were withheld until there was objective evidence (specimen-initiated group) had similar outcome rankings to patients where antibiotics were started immediately. This confirms the findings of the TARPP pilot trial and further gives evidence for equipoise between these two treatment strategies Disclosures Robert G. Sawyer, MD, AbbVie: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant

Background: The practice of rapidly initiating antibiotic therapy for patients with suspected infection has recently been criticized yet remains commonplace. Provider comfort level has been an understudied aspect of this practice.Hypothesis: We hypothesized that there would be no significant differences in provider comfort level between the two treatment groups.Methods: We prospectively surveyed critical care intensivists who provided care for patients enrolled in the Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP), which was a multicenter cluster-randomized crossover trial that evaluated an immediate antibiotic initiation protocol compared with a protocol of specimen-initiated antibiotic initiation in ventilated patients with suspected new-onset pneumonia. At the end of each enrollment arm, physicians at each center were surveyed regarding their overall comfort level with the recently completed treatment arm, and perception of adherence. Both a paired and unpaired analysis was performed.Results: We collected 51 survey responses from 31 unique participants. Providers perceived a higher rate of adherence to the immediate initiation arm than the specimen-initiated arm (Always Adherent: 37.5% vs. 11.1%; p = 0.045). Providers were less comfortable waiting for objective evidence of infection in the specimen-initiated arm than with starting antibiotic agents immediately (Very Comfortable: 83.3% vs. 40.7%; p = 0.004). For the smaller paired analysis, there was no longer a difference in comfort level.Conclusions: There may be differences in provider comfort levels and perceptions of adherence when considering two different antibiotic initiation strategies for suspected pneumonia in ventilated patients. These findings should be considered when planning future studies.

Introduction: Alcohol withdrawal syndrome (AWS) is associated with increased morbidity and mortality in the trauma population. Benzodiazepines (BZD) are standard of care for AWS; however, given the risk of delirium with BZDs and reports of BZD-refractory withdrawal, phenobarbital (PHB) has emerged as an alternative. Safety and efficacy studies of PHB for AWS in trauma patients are lacking. Our aim is to compare a BZD versus PHB regimen in the management of AWS in trauma patients. Methods: We performed a retrospective cohort study at a level 1 trauma center of patients at risk for AWS managed with either a BZD or a low dose oral PHB regimen. Patients were excluded if they were taking a study medication prior to admission, receiving propofol or dexmedetomidine prior to initiation of the study drug, presenting with delirium tremens or seizures, died, or were discharged within 24 hours of presentation. The primary outcome was complicated AWS (seizures or alcohol withdrawal delirium/delirium tremens). Secondary outcomes included uncomplicated AWS, therapy escalation, oversedation, delirium-, ICU-, and ventilator-free days, and length of stay (LOS). Results: 411 patients were identified; 118 received BZD, and 293 received PHB. The odds of developing complicated AWS with PHB versus BZD-based therapy was not statistically significant (OR 0.62; 95% CI, 0.23-1.69); however, patients in the PHB group were less likely to develop uncomplicated AWS (OR 0.09; 95% CI, 0.05-0.17) or require escalation of therapy (OR 0.47; 95% CI, 0.24-0.9). The PHB group had a LOS 3.26 days shorter than the BZD group (p=0.001). There was no difference in ICU-, ventilator-, or delirium-free days. Conclusions: PHB is a safe and effective alternative to BZD-based regimens in the management of AWS in trauma patients.

BACKGROUND: Pneumonia is the most common intensive care unit-acquired infection in the trauma and emergency general surgery population. Despite guidelines urging rapid antibiotic use, data supporting immediate antibiotic initiation in cases of suspected infection are limited. Our hypothesis was that a protocol of specimen-initiated antibiotic initiation would have similar compliance and outcomes to an immediate initiation protocol. METHODS: We devised a pragmatic cluster-randomized crossover pilot trial. Four surgical and trauma intensive care units were randomized to either an immediate initiation or specimen-initiated antibiotic protocol for intubated patients with suspected pneumonia and bronchoscopically obtained cultures who did not require vasopressors. In the immediate initiation arm, antibiotics were started immediately after the culture regardless of patient status. In the specimen-initiated arm, antibiotics were delayed until objective Gram stain or culture results suggested infection. Each site participated in both arms after a washout period and crossover. Outcomes were protocol compliance, all-cause 30-day mortality, and ventilator-free alive days at 30 days. Standard statistical techniques were applied. RESULTS: A total of 186 patients had 244 total cultures, of which only the first was analyzed. Ninety-three patients (50%) were enrolled in each arm, and 94.6% were trauma patients (84.4% blunt trauma). The median age was 50.5 years, and 21% of the cohort was female. There were no differences in demographics, comorbidities, sequential organ failure assessment, Acute Physiology and Chronic Health Evaluation II, or Injury Severity Scores. Antibiotics were started significantly later in the specimen-initiated arm (0 vs. 9.3 hours; p < 0.0001) with 19.4% avoiding antibiotics completely for that episode. There were no differences in the rate of protocol adherence, 30-day mortality, or ventilator-free alive days at 30 days. CONCLUSION: In this cluster-randomized crossover trial, we found similar compliance rates between immediate and specimen-initiated antibiotic strategies. Specimen-initiated antibiotic protocol in patients with a suspected hospital-acquired pneumonia did not result in worse clinical outcomes compared with immediate initiation.

BACKGROUND:Alcohol withdrawal syndrome (AWS) is associated with increased morbidity and mortality in the trauma population. Benzodiazepines (BZDs) are standard of care for AWS; however, given the risk of delirium with BZDs and reports of BZD-refractory withdrawal, phenobarbital (PHB) has emerged as an alternative therapy for AWS. Safety and efficacy studies of PHB for AWS in trauma patients are lacking. Our aim was to compare a BZD versus PHB protocol in the management of AWS in trauma patients. METHODS:We performed a retrospective cohort study at a level 1 trauma center of patients at risk for AWS managed with either a BZD or a low-dose oral PHB regimen. Patients were excluded if they were taking BZDs or barbiturates before admission, received propofol or dexmedetomidine before initiation of the study drug, presented with delirium tremens or seizures, or died or discharged within 24 hours of presentation. The primary outcome was complicated AWS (seizures or alcohol withdrawal delirium/delirium tremens). Secondary outcomes included uncomplicated AWS; therapy escalation; oversedation; delirium-, intensive care unit-, and ventilator-free days; and length of stay. RESULTS:A total of 411 patients were identified; 118 received BZD, and 293 received PHB. The odds of developing complicated AWS with PHB versus BZD-based therapy were not statistically significant (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.21-1.39); however, patients receiving PHB were less likely to develop uncomplicated AWS (OR, 0.08; 95% CI, 0.04-0.14) and less likely to require escalation of therapy (OR, 0.45; 95% CI, 0.24-0.84). The PHB group had a length of stay 3.1 days shorter than the BZD group ( p = 0.002). There was no difference in intensive care unit-, ventilator-, or delirium-free days. CONCLUSION:A PHB-based protocol for the management of AWS is a safe and effective alternative to BZD-based regimens in trauma patients. LEVEL OF EVIDENCE:Therapeutic/Care Management; Level IV.

Background Postoperative ileus (POI) is a surgical complication resulting in increased morbidity and length of stay (LOS). Usual care for POI includes bowel rest and gastric decompression. It has been questioned if methylnaltrexone (MNTX), a peripheral opioid antagonist, could be used as treatment for POI. The purpose of this study was to determine if MNTX is effective and safe for POI treatment. Methods This single-center, retrospective cohort study included patients ⩾ 18 years with a POI. Patients with acute colonic pseudo-obstruction, small bowel obstruction, and gastrointestinal malignancy were excluded. The intervention was MNTX administration. The primary outcome was time to ileus resolution. Secondary outcomes included LOS, duration of nasogastric tube, total parenteral nutrition requirement, and incidence of gastrointestinal perforations. Results 110 patients were included in the analysis; 28 received MNTX. Time to ileus resolution was 9.9 days for the MNTX group and 11.4 days for the control group ( P = .38). Duration of gastric decompression was 4.6 days for the MNTX group and 4.2 days for the control group ( P = .71). Length of stay was 19.9 days for the MNTX group and 19.7 days for the control group ( P = .96). The percentage of TPN requirement was 17.9% in the MNTX group and 22.0% in the control group ( P = .65). No gastrointestinal perforations were observed in either group. Conclusion For the treatment of POI, MNTX did not significantly reduce time to resolution of ileus, LOS, duration of gastric decompression, or TPN requirements. However, no gastrointestinal perforations were seen, indicating that MNTX may be safely used in these patients.

Prior studies in critically ill patients suggest the supra-physiologic chloride concentration of 0.9% (“normal”) saline may be associated with higher risk of renal failure and death compared to physiologically balanced crystalloids. However, the comparative effects of 0.9% saline and balanced fluids are largely unexamined among patients outside the intensive care unit, who represent the vast majority of patients treated with intravenous fluids.

Barrett, Tyler W. MD, MSCI; Wrenn, Keith D. MD; Slovis, Corey M. MD; Jones, Ian D. MD; Wright, Patty W. MD; Self, Wesley H. MD, MPH; Russ, Stephan MD MPH; Collins, Sean P. MD, MS; Ward, Michael J. MD, MBA; Felbinger, Matthew PharmD, BCPS; Atchison, Leanne PharmD; Beckman, Joshua A. MD Author Information