Prone Positioning in Severe Acute Respiratory Distress Syndrome

978 exposure incidents. The most severe case involved a 29-year-old man who intravenously injected 3 mL of an unknown concentration of 25I-NBOME that he had purchased from a ‘‘dealer’’ in liquid form, who presented with agitation, aggression, seizures, and respiratory failure. The hospital course included development of acute kidney injury secondary to rhabdomyolysis requiring continuous veno-venous hemofiltration, as well as the development of acute respiratory distress syndrome requiring prone ventilation. Ultimately, the patient was transferred from the intensive care unit on hospital day 38, after his renal function had normalized, and he was discharged from the hospital days later without any chronic sequelae. Cases 2–7 involved a group of men, aged 19–22 years, who used 25INBOMe together after it had been purchased in powder form via the Internet. Case 2, a 20-year-old man on fluoxetine, had the most severe symptoms, developing serotonin syndrome that responded well to cyproheptadine. Cases 3–7 were similar, presenting with aggression, agitation, and visual and auditory hallucinations that were successfully managed with benzodiazepines, and resolved over 15 h of observation. In summary, clinical features included tachycardia (n = 7), hypertension (n = 4), agitation (n = 6), aggression (n = 5), visual and auditory hallucination (n = 6), seizures (n = 3), hyperpyrexia (n = 3), clonus (n = 2), leukocytosis (n = 2), elevated creatine kinase (n = 7), metabolic acidosis (n = 3), respiratory failure (n = 2), and acute kidney injury (n = 1). Severe toxicity can result after 25I-NBOMe abuse, with stimulant and serotoninergic effects predominating. Clinicians should be alert to this substance with its emergence in both the United States and Europe. [W. Gannon Sungar, DO Denver Health Medical Center, Denver, CO] Comments: 25I-NBOME is a novel sympathomimetic agent with extremely potent serotoninergic effects, a narrow safety window, and a consequent high risk of inadvertent overdose. This case series shows the capacity for severe toxicity with intravenous administration of 25I-NBOMe, especially in the setting of concomitant selective serotonin reuptake inhibitor use. , SAFETY OF INTRAHOSPITAL TRANSPORT IN VENTILATED CRITICALLY ILL PATIENTS: A MULTICENTER COHORT STUDY. Schwebel C, Clec’h C, Magne S, Minet C, et al. Crit Care Med 2013;41:1919–28. This matched prospective cohort study aimed to identify complications associated with intrahospital transport of critically ill patients who required mechanical ventilation. Data were obtained from the OUTCOMEREA study group, a French group that collects outcome data on patients admitted to participating French intensive care units (ICUs). Patients 18 years or older admitted to a participating ICU between April 2000 and November 2010 and requiring intubation were included in the study. Intrahospital transport (IHT) was defined as the transport of a patient to any site located outside the ICU but within the hospital (excluding transport to an operating room). Exposed (transported) patients were matched up to four unexposed (nontransported) patients according to gender, age, weight, chronic

Abstracts comorbidities, admission diagnosis, ICU length of stay prior to transport, and a calculated propensity score of being transported. Adjustment was made for confounding factors present on the day prior to IHT (such as central and arterial catheters, urinary catheters, and drains). During this study period, 6242 ICU patients required mechanical ventilation. Of these, 1782 patients had 3006 IHTs other than to an operating room (1–17 IHTs/patient). The majority of IHTs were to the CT scanner (93.6%). A total of 1659 intrahospital transport patients were matched to 3344 nonintrahospital transport patients. After adjustment for confounding variables, IHT patients were found to be at higher risk for a variety of complications. Specifically, these patients were at higher risk of deep venous thrombosis (odds ratio [OR] 4.5; 95% confidence interval [CI] 1.9–10.6; p = 0.0006); respiratory events, such as pneumothorax (OR 2.6; 95% CI 1.4–4.9; p = 0.004), atelectasis (OR 2.9; 95% CI, 1.4–5.9; p = 0.004), ventilator-associated pneumonia (OR 1.4; 95% CI 1.1–1.8; p = 0.02), and metabolic events, such as hypoglycemia (OR 2.3; 95% CI 1.5–3.5; p = 0.0001), hyperglycemia (OR 2.3; 95% CI 1.9–2.7; p < 0.0001), and hypernatremia (OR 1.6; 95% CI 1.3–1.9; p < 0.0001). In addition, transported patients had a 4–11-day increase in ICU length of stay (OR 1.5; 95% CI 1.3–1.8, p < 0.0001). However, 28-day mortality was not significantly affected (OR 0.9; 95% CI 0.8-1.0; p = 0.08). The authors concluded that critically ill patients requiring mechanical ventilation experience more complications if transported outside the ICU than nontransported patients. [Jessica Slim, MD Denver Health Medical Center, Denver, CO] Comments: Although it seems intuitive that patients who require intensive care are better served by remaining in the ICU, this article does not definitively establish causality between transport outside of the ICU and a variety of complications. The main confounder that the authors did not account for was the severity of illness of the patients; those who were sicker were more likely to require transport for tests and also more likely to experience complications. Nonetheless, the results are cautionary for the transport of critically ill patients outside of the ED. , PRONE POSITIONING IN SEVERE ACUTE RESPIRATORY DISTRESS SYNDROME. Guerin C, Reignier J, Richard J-C, et al. N Engl J Med 2013;368:2159–67. This multicenter, prospective, randomized controlled trial assigned 466 patients with severe acute respiratory distress syndrome (ARDS; defined as partial pressure of arterial oxygen [PaO2] to fraction of inspired oxygen [FiO2] ratio < 150 mm Hg, FiO2 > 0.6, positive end expiratory pressure [PEEP] $ 5, tidal volume close to 6 mL per kilogram of predicted body weight) to one of two groups: supine ventilation and prone-positioning ventilation (of at least 16 h). The primary outcome in this study was 28-day mortality; the secondary outcome was 90-day mortality. The 28-day mortality in the prone group was 16%, vs. 32.8% in the supine group (p < 0.001; absolute risk reduction 17%, relative risk reduction [RRR] 50%). The 90-day mortality was 23.6% in the prone group, vs. 41% in

The Journal of Emergency Medicine the supine group (p < 0.001). The authors concluded that prolonged prone-positioning ventilation sessions significantly reduce 28-day and 90-day mortality in patients with severe ARDS. [David Otten, MD Denver Health Medical Center, Denver, CO] Comments: The main limitation of this study is its small size. Although well designed and seemingly well done, the results of the study raise questions. Prior studies investigating the use of prone ventilation in patients with ARDS failed to show a benefit. Yet in this study, an absolute risk reduction of more than 10% was demonstrated (RRR = 51%!). When a study is so overwhelmingly positive in the face of so many negative studies that came before it, one needs to ask why this is and await reproduction of the results before accepting these findings.

, RAPID BLOOD-PRESSURE LOWERING IN PATIENTS WITH ACUTE INTRACEREBRAL HEMORRHAGE. Anderson CS, Heeley E, Huang Y, et al. N Engl J Med 2013;368:2355–65. This multicenter randomized controlled trial compared current guideline-recommended systolic blood pressure (SBP) control of < 180 mm Hg for hypertensive patients after acute intracerebral hemorrhage (ICH) to an intensive strategy targeting SBP of < 140 mm Hg. Patients were included if the ICH onset was within 6 h of presentation, and if they were hypertensive with SBP of 150–220 mm Hg. Patients were excluded if they had a Glasgow Coma Scale score of < 6, if they had a massive hematoma with poor prognosis, or if early surgery was planned. Intensive SBP intervention targeted a goal of < 140 mm Hg within 1 h of randomization using intravenous (i.v.) and oral therapy, depending on local availability. Standard therapy consisted of using i.v. or oral medications any time the patient’s SBP was > 180 mm Hg, with no lower limit. Primary outcome was death or major disability using the modified Rankin scale at 90 days. Secondary outcomes included physical function across all seven levels of the modified Rankin scale, all-cause mortality and cause-specific mortality, and five dimensions of health-related quality of life (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) using a questionnaire. There were 2839 patients randomly assigned to standard or intensive blood pressure control. Mean SBP levels were significantly different between 15 min and 7 days post randomization. With respect to the intensive control group, mean SBP at 1 h was 150 mm Hg, with 33.4% achieving the goal SBP of < 140 mm Hg within 1 h as compared to a mean of 164 mm Hg in the standard-treatment group. At 90 days, 52% in the intensive-treatment group as compared to 55.6% in the standard-treatment group had the primary outcome of death or major disability (confidence interval [CI] 0.75–1.01, p = 0.06). Ordinal analysis revealed a shift toward favorable Rankin scores in the intensive SBP control group (CI 0.77– 1.00, p = 0.04). Participants in the intensive-treatment arm reported significantly better health-related quality of life using the five-dimension questionnaire, and the rate of all-cause death

979 was not significantly different, nor was the rate of death from the ICH. Difference in hematoma size between the two groups at 24 h in a subgroup analysis was not significant. [Corey Siebe, MD Denver Health Medical Center, Denver, CO] Comment: This well-designed study failed to demonstrate any difference in the primary outcome with standard or intensive blood pressure control in patients with ICH. Although there was a trend toward improvement in the secondary outcomes, a different, properly powered study would have to be done to quantify this effect and help guide emergency physicians as to how to best manage blood pressure in these patients. , RACEMIC ADRENALINE AND INHALATION STRATEGIES IN ACUTE BRONCHIOLITIS. Skjerven HO, Gjengsto Hunderi JO, Brugmann-Pieper SK, et al. N Engl J Med 2013;368:2286–93. Acute bronchiolitis in infants frequently leads to hospitalization. Despite the burden of this disease, there is no established consensus on inhalation therapy. This multicenter, randomized, double-blind clinical trial compared inhaled racemic epinephrine with inhaled saline, and on-demand inhalation with fixed-schedule inhalation in infants (< 12 months) with moderate-to-severe acute bronchiolitis. The primary outcome was the length of hospital stay, and secondary outcomes included change in clinical score 30 min after the first inhalation, use of nasogastric tube feeding, oxygen supplementation, and ventilator support. Four hundred four (59.4% male) children with a mean age of 4.2 months were enrolled, on hospital admission, from eight hospitals in Norway from January 2010 to May 2011. Inclusion criteria were clinical signs of bronchiolitis, age < 12 months, and a clinical score of at least 4 on a scale of 0–10. Clinical score was calculated by a pediatrician, composed of the sum of points allotted from 0 (normal) to 2 (severe illness) for the following clinical variables: general condition, skin color, auscultatory findings, respiratory rate, and retractions. Exclusion criteria were presence of serious cardiac, immunologic, neurologic, oncologic, or preceding pulmonary disease; more than one prior episode of obstructive airway disease; coughing for more than 4 weeks; and glucocorticoid therapy in the preceding 4 weeks. Subjects were randomized to receive either inhaled epinephrine or inhaled normal (0.9%) saline on either a fixed (not described) or on-demand treatment schedule, resulting in a total of four study groups. There was no significant difference in any of the primary or secondary outcomes in infants treated with inhaled racemic epinephrine vs. inhaled saline (p > 0.1 for all comparisons). Additionally, history of atopic eczema or wheezing, family history of atopic disease, and sex had no significant influence on treatment response. On-demand inhalation was associated with a significantly shorter estimated length of stay – 47.6 h (95% confidence interval [CI] 30.6–64.6) vs. 61.3 h (95% CI 45.4–77.2, p = 0.01) – as well as less use of oxygen supplementation, less use of ventilator support, and fewer inhalation treatments (12.0 vs. 17.0, p < 0.001) when compared to fixed-schedule treatments. The study medication was discontinued in 83 children (20.5%),