Barry Milcarek

Association Between Arterial Hyperoxia Following Resuscitation From Cardiac Arrest and In-Hospital Mortality

CONTEXT Laboratory investigations suggest that exposure to hyperoxia after resuscitation from cardiac arrest may worsen anoxic brain injury; however, clinical data are lacking. OBJECTIVE To test the hypothesis that postresuscitation hyperoxia is associated with increased mortality. DESIGN, SETTING, AND PATIENTS Multicenter cohort study using the Project IMPACT critical care database of intensive care units (ICUs) at 120 US hospitals between 2001 and 2005. Patient inclusion criteria were age older than 17 years, nontraumatic cardiac arrest, cardiopulmonary resuscitation within 24 hours prior to ICU arrival, and arterial blood gas analysis performed within 24 hours following ICU arrival. Patients were divided into 3 groups defined a priori based on PaO(2) on the first arterial blood gas values obtained in the ICU. Hyperoxia was defined as PaO(2) of 300 mm Hg or greater; hypoxia, PaO(2) of less than 60 mm Hg (or ratio of PaO(2) to fraction of inspired oxygen <300); and normoxia, not classified as hyperoxia or hypoxia. MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Of 6326 patients, 1156 had hyperoxia (18%), 3999 had hypoxia (63%), and 1171 had normoxia (19%). The hyperoxia group had significantly higher in-hospital mortality (732/1156 [63%; 95% confidence interval {CI}, 60%-66%]) compared with the normoxia group (532/1171 [45%; 95% CI, 43%-48%]; proportion difference, 18% [95% CI, 14%-22%]) and the hypoxia group (2297/3999 [57%; 95% CI, 56%-59%]; proportion difference, 6% [95% CI, 3%-9%]). In a model controlling for potential confounders (eg, age, preadmission functional status, comorbid conditions, vital signs, and other physiological indices), hyperoxia exposure had an odds ratio for death of 1.8 (95% CI, 1.5-2.2). CONCLUSION Among patients admitted to the ICU following resuscitation from cardiac arrest, arterial hyperoxia was independently associated with increased in-hospital mortality compared with either hypoxia or normoxia.

Relationship Between Supranormal Oxygen Tension and Outcome After Resuscitation From Cardiac Arrest

Background— Laboratory and recent clinical data suggest that hyperoxemia after resuscitation from cardiac arrest is harmful; however, it remains unclear if the risk of adverse outcome is a threshold effect at a specific supranormal oxygen tension, or is a dose-dependent association. We aimed to define the relationship between supranormal oxygen tension and outcome in postresuscitation patients. Methods and Results— This was a multicenter cohort study using the Project IMPACT database (intensive care units at 120 US hospitals). Inclusion criteria were age >17 years, nontrauma, cardiopulmonary resuscitation preceding intensive care unit arrival, and postresuscitation arterial blood gas obtained. We excluded patients with hypoxia or severe oxygenation impairment. We defined the exposure by the highest partial pressure of arterial oxygen (PaO2) over the first 24 hours in the ICU. The primary outcome measure was in-hospital mortality. We tested the association between PaO2 (continuous variable) and mortality using multivariable logistic regression adjusted for patient-oriented covariates and potential hospital effects. Of 4459 patients, 54% died. The median postresuscitation PaO2 was 231 (interquartile range 149 to 349) mm Hg. Over ascending ranges of oxygen tension, we found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis, a 100 mm Hg increase in PaO2 was associated with a 24% increase in mortality risk (odds ratio 1.24 [95% confidence interval 1.18 to 1.31]. We observed no evidence supporting a single threshold for harm from supranormal oxygen tension. Conclusion— In this large sample of postresuscitation patients, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.

Residency Curriculum Improves Breastfeeding Care

OBJECTIVES: Multiple studies have revealed inadequacies in breastfeeding education during residency, and results of recent studies have confirmed that attitudes of practicing pediatricians toward breastfeeding are deteriorating. In this we study evaluated whether a residency curriculum improved physician knowledge, practice patterns, and confidence in providing breastfeeding care and whether implementation of this curriculum was associated with increased breastfeeding rates in patients. SUBJECTS AND METHODS: A prospective cohort of 417 residents was enrolled in a controlled trial of a novel curriculum developed by the American Academy of Pediatrics in conjunction with experts from the American College of Obstetricians and Gynecologists, American Academy of Family Physicians, and Association of Pediatric Program Directors. Six intervention residency programs implemented the curriculum, whereas 7 control programs did not. Residents completed pretests and posttests before and after implementation. Breastfeeding rates were derived from randomly selected medical charts in hospitals and clinics at which residents trained. RESULTS: Trained residents were more likely to show improvements in knowledge (odds ratio [OR]: 2.8 [95% confidence interval (CI): 1.5–5.0]), practice patterns related to breastfeeding (OR: 2.2 [95% CI: 1.3–3.7]), and confidence (OR: 2.4 [95% CI: 1.4–4.1]) than residents at control sites. Infants at the institutions in which the curriculum was implemented were more likely to breastfeed exclusively 6 months after intervention (OR: 4.1 [95% CI: 1.8–9.7]). CONCLUSIONS: A targeted breastfeeding curriculum for residents in pediatrics, family medicine, and obstetrics and gynecology improves knowledge, practice patterns, and confidence in breastfeeding management in residents and increases exclusive breastfeeding in their patients. Implementation of this curriculum may similarly benefit other institutions.

Hypofractionated stereotactic radiotherapy for the treatment of brain metastases.

This retrospective review evaluated the efficacy and toxicity profiles of various dose fractionations using hypofractionated stereotactic radiotherapy (HSRT) in the treatment of brain metastases.

Removal of Industry-Sponsored Formula Sample Packs from the Hospital: Does It Make a Difference?

Background: Most US hospitals distribute industry-sponsored formula sample packs. No research has examined outcomes associated with sample pack removal as part of a hospital intervention to eliminate sample distribution postpartum. Objective: To examine prospectively hospital-based and breastfeeding outcomes associated with removal of industry-sponsored formula sample packs from the hospital. Methods: We enrolled mothers postpartum at Cooper University Hospital, an urban New Jersey hospital, in 2009-2010. For the first 6 months, all women received industry-sponsored formula samples packs (control group); for the next 6 months, all postpartum women received hospital-sponsored bags with no formula at source (intervention group). Research assistants blinded to the design called subjects weekly for 10 weeks to determine feeding practices. Results: We enrolled 527 breastfeeding women (284 control; 243 intervention). At 10 weeks postpartum, 82% of control and 36% of intervention women (P < .001) reported receiving formula in the “diaper discharge bag.” Kaplan-Meyer curves for any breastfeeding showed the intervention was associated with increased breastfeeding (P = .03); however, exclusive breastfeeding was not significantly different between intervention and controls (P = .46). In post hoc analysis, receiving no take-home formula in bottles from the hospital was associated with increased exclusive breastfeeding in control (P = .02) and intervention (P = .03) groups at 10 weeks. Conclusion: Although the hospital-branded replacement contained no formula at source, many women reported receiving bottles of formula from the hospital. Change in practice to remove industry-sponsored formula sample packs was associated with increased breastfeeding over 10 weeks, but the intervention may have had a greater impact had it not been contaminated.

Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer

The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer.

Betamethasone dosing interval: 12 or 24 hours apart? A randomized, noninferiority open trial

OBJECTIVE We sought to determine whether the incidence of neonatal respiratory distress syndrome (RDS) is similar with 12- vs 24-hour dosing interval of betamethasone. STUDY DESIGN This was a prospective, randomized, open, noninferiority trial. Mothers (n = 228) with a singleton or multiple pregnancies (fetuses = 260), between gestational age of 23-34 weeks, at risk for preterm delivery, received standard 2 doses of betamethasone either 12 or 24 hours apart in 2:1 ratio, respectively. RESULTS Incidence of RDS was similar in the 2 cohorts (36.5% vs 37.3%; P = not significant). Women unable to receive the complete course of corticosteroids with the 24-hour interval can be reduced by half with the 12-hour interval. However, increased incidence of necrotizing enterocolitis was seen with 12-hour dosing (6.2% vs 0%; P = .03). CONCLUSION The 12-hour dosing interval is equivalent to the 24-hour dosing interval for prevention of RDS in neonates of mothers delivering prematurely. A larger multicenter study is needed to confirm our findings.

Therapeutic hypothermia and vasopressor dependency after cardiac arrest

OBJECTIVE Clinical trials of therapeutic hypothermia (TH) after cardiac arrest excluded patients with persistent hemodynamic instability after return of spontaneous circulation (ROSC), and thus equipoise may exist regarding use of TH in these patients. Our objective was to determine if TH is associated with worsening hemodynamic instability among patients who are vasopressor-dependent after ROSC. METHODS We performed a prospective observational study in vasopressor-dependent post-cardiac arrest patients. Inclusion criteria were age >17, non-trauma cardiac arrest, comatose after ROSC, and persistent vasopressor dependence. The decision to initiate TH (33-34 ° C) was made by the treating physician. We measured cumulative vasopressor index (CVI) and mean arterial pressure (MAP) every 15 min during the first 6h after ROSC. The outcome measures were change in CVI (primary outcome) and MAP (secondary outcome) over time. We graphed median CVI and MAP over time for the treated and not treated cohorts, and used propensity adjusted repeated measures mixed models to test for an association between TH induction and change in CVI or MAP over time. RESULTS Seventy-five post-cardiac arrest patients were included (35 treated; 40 not treated). We observed no major differences in CVI or MAP over time between the treated and not treated cohorts. In the mixed models we found no statistically significant association between TH induction and changes in CVI or MAP. CONCLUSION In patients with vasopressor-dependency after cardiac arrest, the induction of hypothermia was not associated with a decrease in mean arterial pressure or increase in vasopressor requirement.

The fallacy of the BUN:creatinine ratio in critically ill patients

BACKGROUND AND OBJECTIVES Acute kidney injury (AKI) is common in critically ill patients and is associated with a high mortality rate. Pre-renal azotemia, suggested by a high blood urea nitrogen to serum creatinine (BUN:Cr) ratio (BCR), has traditionally been associated with a better prognosis than other forms of AKI. Whether this pertains to critically ill patients is unknown. METHODS We conducted a retrospective observational study of two cohorts of critically ill patients admitted to a single center: a derivation cohort, in which AKI was diagnosed, and a larger validation cohort. We analyzed associations between BCR and clinical outcomes: mortality and renal replacement therapy (RRT). RESULTS Patients in the derivation cohort (N = 1010) with BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was significantly associated with increased mortality and a lower likelihood of RRT in all patients, patients with AKI and patients at risk for AKI. Patients in the validation cohort (N = 10 228) with a BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was associated with increased mortality and a lower likelihood of RRT in all patients and in those at risk for AKI, BUN correlated with age and severity of illness. CONCLUSIONS A BCR >20 is associated with increased mortality in critically ill patients. It is also associated with a lower likelihood of RRT, perhaps because of misinterpretation of the BCR. Clinicians should not use a BCR >20 to classify AKI in critically ill patients.

Prevalence and impact of anemia in hospitalized patients.

Objective The prevalence of anemia is increasing in the general population similarly to other comorbidities and is associated with high mortality in a variety of settings. Most studies, however, have analyzed older adults or specific comorbidities, and the independent impact of anemia on outcomes in a general population of hospitalized patients has not been clearly defined. Methods Retrospective analysis of a medical records database of all consecutive patient discharges (aged 18 years or older) admitted to our institution from January 1, 1999 through December 31, 2008. Results A total of 179,516 admissions were included. Of these, 18,589 patients were diagnosed as having anemia (10.4%). There were 123,586 patients younger than 65 years. The prevalence of anemia among all of the discharges was characterized by a significant linear increase across the 10-year time frame, from 8.7% (1999) to 12.8% (2008), as was the average number of comorbidities. Over time, anemic patients were characterized by increasing comorbidity. Anemia was significantly associated with mortality (6.5% vs 2.5%; P < 0.001, odds ratio 2.68). This association remained significant after additional adjustment for demographic characteristics and comorbidities. The risk of mortality was significantly higher in patients younger than 65 years than it was in patients older than 65 (odds ratio 3.2 vs 2.1, respectively). Conclusions The prevalence of anemia increased during a 10-year time frame, as did the average number of associated comorbid conditions. With adjustment for time, demographic factors, and additional comorbidities, anemia remained independently associated with mortality. This association was stronger in younger patients.