Early Interventions for the Prevention of Posttraumatic Stress Symptoms in Survivors of Critical Illness: A Qualitative Systematic Review.

OBJECTIVES: Posttraumatic stress disorder among survivors of critical illness is of public health importance, as it is common and reduces patient quality of life. The objective of this systematic review was to collate the world's literature on interventions aimed at preventing posttraumatic stress disorder among survivors of critical illness. DATA SOURCES: We performed a search of CENTRAL, MEDLINE, EMBASE, CINAHL, and clinical trials registry platforms, with no restriction to language using a comprehensive strategy. STUDY SELECTION: Study inclusion criteria were as follows: 1) adult human subjects, 2) patients treated in an ICU setting, 3) intervention arm aimed at reducing posttraumatic stress disorder symptoms, 4) use of a control arm, and 5) an outcome measure assessing development of acute stress or posttraumatic stress disorder symptoms. DATA EXTRACTION: We performed a qualitative analysis to collate and summarize effects of identified interventions according to the recommended methodology from the Cochrane Handbook. DATA SYNTHESIS: Seventeen studies met all inclusion and no exclusion criteria. There was heterogeneity in interventions and outcome measures used. All studies had some concern for risk of bias as per the Cochrane tool for assessing risk of bias. In eight of 12 studies (67%) testing early interventions (i.e., initiated in the ICU course) and one of five studies (20%) testing delayed interventions following ICU discharge, posttraumatic stress disorder symptoms were decreased among the intervention group compared with controls. CONCLUSIONS: Despite a paucity of high-quality clinical investigations, the preponderance of evidence to date suggests that 1) posttraumatic stress disorder among survivors of critical illness may be preventable and 2) early interventions may be the most effective.

Early interventions for the prevention of post-traumatic stress symptoms in survivors of critical illness: protocol for a systematic review.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is being increasingly reported among survivors of critical illness and injury. Previous work has demonstrated that PTSD reduces patient quality of life and ability to return to work, as well as increases healthcare costs. As such, identifying interventions aimed at preventing the development of critical illness-related PTSD could have an important public health impact. The objective of this systematic review is to collate the world's literature on early interventions aimed at preventing PTSD among survivors of critical illness. METHODS AND ANALYSIS: We will perform a qualitative systematic review of human clinical trials of interventions aimed at preventing or reducing critical illness-related PTSD symptoms. We will methodically search CENTRAL, MEDLINE, Embase and CINAHL. We will also search websites containing details on clinical trials registration (National Library of Medicine's ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform), as well as screen reference lists of the articles we select for inclusion to identify additional studies for potential inclusion. Two authors will independently review all search results. After identification and inclusion of articles, we will use a standardised form for data extraction. We will use tables to describe the study type, populations, interventions tested and timing of interventions, outcome measures and effects of interventions on outcome measures compared with control groups. This review will be completed between 1 August 2017 and 31 August 2017. ETHICS AND DISSEMINATION: The proposed systematic review will not collect individual patient level data and does not require ethical approval. Results of this study will contribute to the understanding of critical illness-related PTSD and help prompt future research aimed at further developing interventions to prevent PTSD symptoms in survivors of critical illness. PROSPERO REGISTRATION NUMBER: This systematic review is registered in the PROSPERO international prospective register of systematic reviews (registration number CRD42017069672).

Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*.

OBJECTIVES: Sepsis treatment guidelines recommend macrocirculatory hemodynamic optimization; however, microcirculatory dysfunction is integral to sepsis pathogenesis. We aimed to test the hypothesis that following macrocirculatory optimization, inhaled nitric oxide would improve microcirculation in patients with sepsis and that improved microcirculation would improve lactate clearance and multiple organ dysfunction. DESIGN: Randomized, sham-controlled clinical trial. SETTING: Single urban academic medical center. PATIENTS: Adult patients with severe sepsis and systolic blood pressure less than 90 mm Hg despite intravascular volume expansion and/or serum lactate greater than or equal to 4.0 mmol/L. INTERVENTIONS: After achievement of macrocirculatory resuscitation goals, we randomized patients to 6 hours of inhaled nitric oxide (40 ppm) or sham inhaled nitric oxide administration. We administered study drug via a specialized delivery device that concealed treatment allocation so that investigators and clinical staff remained blinded. MEASUREMENTS AND MAIN RESULTS: We performed sidestream dark-field videomicroscopy of the sublingual microcirculation prior to and 2 hours after study drug initiation. The primary outcome measure was the change in microcirculatory flow index. Secondary outcomes were lactate clearance and change in Sequential Organ Failure Assessment score. We enrolled 50 patients (28 of 50 [56%] requiring vasopressor agents; 15 of 50 [30%] died). Although inhaled nitric oxide significantly raised plasma nitrite levels, it did not improve microcirculatory flow, lactate clearance, or organ dysfunction. In contrast to previous studies conducted during the earliest phase of resuscitation, we found no association between changes in microcirculatory flow and lactate clearance or organ dysfunction. CONCLUSIONS: Following macrocirculatory optimization, inhaled nitric oxide at 40 ppm did not augment microcirculatory perfusion in patients with sepsis. Further, we found no association between microcirculatory perfusion and multiple organ dysfunction after initial resuscitation.

Use and efficacy of nebulized naloxone in patients with suspected opioid intoxication.

OBJECTIVE: To describe the use and efficacy of nebulized naloxone in patients with suspected opioid intoxication. METHODS: This was an observational study conducted at an inner city emergency department. Patients were eligible if they had self-reported or suspected opioid intoxication and a spontaneous respiratory rate ≥6 breaths/minute. Nebulized naloxone (2 mg in 3 mL normal saline) was administered through a standard face mask at the discretion of the treating physician. Structured data collection included demographics, vital signs pre and post naloxone administration and adverse events. The primary outcome was level of consciousness, which was recorded pre and 15 minutes postnaloxone administration using the Glasgow Coma Scale (GCS) and the Richmond Agitation Sedation Scale (RASS). RESULTS: Of the 73 patients who presented with suspected opioid intoxication and were given naloxone over the study period, 26 were initially treated with nebulized naloxone. After nebulized naloxone administration, median GCS improved from 11 [interquartile range (IQR) 3.5] to 13 (IQR, 2.5), P = .001. Median RASS improved from -3.0 (IQR, -1.0) to -2.0 (IQR, -1.5), P < .0001. Need for supplemental oxygen decreased from 81% to 50%, P = .03. Vital signs did not differ pre/post therapy. There were few adverse effects from nebulized naloxone administration: 12% experienced moderate-severe agitation, 8% were diaphoretic and none vomited. Eleven required subsequent administrations of naloxone, nine of whom self-reported using either heroin, methadone or both. Of these, 5 underwent urine drug screening and all 5 tested positive for either opiates or methadone. CONCLUSIONS: Nebulized naloxone was well-tolerated and led to a reduction in the need for supplemental oxygen as well as improved median GCS and RASS scores in patients with suspected opioid intoxication.

The impact of crowding on time until abdominal CT interpretation in emergency department patients with acute abdominal pain.

OBJECTIVE: We assessed the relationship between emergency department (ED) crowding and delays in care in patients presenting with abdominal pain who receive abdominal computed tomography (CT). METHODS: Prospective cohort study of adults who presented over a 1-year period to 2 urban academic EDs with abdominal pain and received CT. Each subject had 3 validated crowding measures assigned at enrollment (ED census, waiting room number, number of admitted patients). These were normalized to quartiles to signify least to most crowded. The Cuzick test was used for trend and log-linear regression and tested the association between ED crowding and time from triage to CT read. The time interval was further decomposed into triage to room, room to CT order, and order to CT read times. The adjusted analysis controlled for age, sex, race, pain score, time of day, triage level, and site. RESULTS: 767 patients were enrolled (mean age, 44 +/- 17 years; 61% female; 60% black). Median time from triage to CT read was 375 minutes (interquartile range [IQR], 276-497). Individual time intervals included triage to room (46 minutes [IQR, 16-111]), room to CT order (83 minutes [IQR, 38-151]), and order to CT read (203 minutes [IQR, 138-375]). Across waiting room quartiles, triage to CT read was associated with progressively longer times (318 vs 364 vs 414 vs 445 minutes; P < 0.001 for trend). Similar trends were noted for waiting room number and admitted patients (P < 0.001). In multivariable analysis, the association between ED crowding and time from triage to CT read remained significant and consistent across all crowding measures (P < 0.001). When decomposed into time intervals, triage to room time showed the greatest difference (22 vs 38 vs 72 vs 92 minutes; P < 0.001). CONCLUSION: ED crowding is associated with an approximately 2-hour delay to CT interpretation availability. Attempts to reduce delays in abdominal CTs may include earlier provider evaluation and placement in the queue for scanning.