Characterizing the Dose Response of Hyperoxia with Brain Perfusion.

BACKGROUND: Tactical aviators require administration of enhanced inspired oxygen concentrations (hyperoxia) to reduce risk of hypobaric hypoxia and decompression injuries. Hyperoxia is not without consequence; it reduces cerebral perfusion (CBF). Characterizing the relationship between FIO2 and CBF is necessary to establish FIO2 levels that do not reduce CBF yet are sufficient to mitigate risk of in-flight physiological stressors. To achieve that goal, this study's objective was to determine whether a dose-response relationship exists between FIO2 and CBF and, if so, the FIO2 at which CBF significantly declines.METHODS: Healthy male and female subjects (N = 26) were randomized to receive either low dose FIO2 of 30%, 40%, 50%, and 100% (Arm 1) or high dose FIO2 of 60%, 70%, 80%, and 100% (Arm 2), followed by a return to 21% for both groups. Subjects were placed within a 3-Tesla MRI scanner equipped with pseudocontinuous arterial spin labeling software (pCASL) to measure CBF. Baseline CBF measurements were obtained during exposure to 21% FIO2, with subsequent CBF measurements obtained at each predetermined FIO2 level.RESULTS: Baseline CBF did not differ between subjects in Arm 1 and Arm 2. Low dose FIO2 ≤ 50% did not affect CBF. In contrast, high dose FIO2 ≥ 60% significantly reduced CBF. Exposure to 100% FIO2 led to similar reductions of CBF for subjects in both Arm 1 and Arm 2.DISCUSSION: The neurovascular system appears to respond to increasing FIO2 levels in a dose dependent manner, with significant reductions in CBF with FIO2 exposures ≥ 60%.Damato EG, Fillioe SJ, Vannix IS, Norton LK, Margevicius SP, Beebe JL, Decker MJ. Characterizing the dose response of hyperoxia with brain perfusion. Aerosp Med Hum Perform. 2022; 93(6):493-498.

Increased Serum Levels of Proinflammatory Cytokines Are Accompanied by Fatigue in Military T-6A Texan II Instructor Pilots.

Tactical aviation imposes unprecedented physical challenges including repetitive exposure to hypergravity, hyperoxia, increased work of breathing, and profound cognitive workloads. Each stressor evokes outcomes ranging from musculoskeletal duress and atelectasis to physical and cognitive fatigue, the latter among the foremost threats to aviators. Whereas sleep loss is traditionally considered the primary cause of fatigue in aviators, converging experimental, observational, and medical studies have identified biochemical mechanisms promoting onset of fatigue. Those mechanisms, which fundamentally differ from sleep loss, revolve around increased proinflammatory cytokines, produced and released in response to tissue injury, chronic inflammatory disorders, allergens, or physical duress. This study's objective was to inform our understanding of potential relationships between serum levels of proinflammatory cytokines and onset of fatigue within a cohort of aviators who experience multiple high-performance sorties on a daily basis. Methods: Active duty and reservist T-6A Texan II instructor pilots were studied on three separate days across their week-long flying schedule. Data collected included a physical assessment, subjective fatigue levels, venous blood samples for measures of chemistry and serum analytes, and urine samples for specific gravity. Results: Twenty-three persons were studied, of which 22 fulfilled minimum study requirements of completing two sorties. The study cohort was comprised of primarily males, age 37.95 ± 4.73 years with a BMI of 26.63 ± 3.15 kg/m2. Of 37 measurable serum analytes, 20 differed significantly (p < 0.05) between baseline values with those measured at the study endpoint. Thirteen of the aviators reported increased fatigue scores across their flying schedule whereas nine did not. Eleven blood serum analytes were associated with increasing levels of fatigue. Discussion: Fatigue in aviators has been attributed almost solely to sleep loss, nocturnal sorties, or disrupted circadian rhythmicity. In contrast, our study findings suggest an alternative mechanism that can promote onset of fatigue: increased blood levels of proinflammatory cytokines. Specific mechanisms triggering synthesis and release of those cytokines and other analytes are yet to be determined. However, their expression patterns suggest responses to both chronic and acute inflammation, hyperoxia, or bronchopulmonary responses to inspiration of dry gas, positive airway pressure, or perhaps atelectasis.

Intestinal Function after Early versus Late Appendectomy in Children with Perforated Appendicitis.

The aim was to prospectively document the impact of early versus late appendectomy on intestinal function in pediatric perforated appendicitis. After Institutional Review Board approval, between September 2016 and August 2017, complete data were prospectively collected for children undergoing planned appendectomy for perforated appendicitis. One hundred children with pathologist-confirmed transmural perforations were included. The median time to operation after pain onset was three days. Operation on day 1 or 2 (early) was compared with that on day 3 or after (late) (range, 3-9 days). Emesis, nasogastric tubes, and time to tolerate diet evaluated intestinal function. Categorical and continuous variables were analyzed by chi-square and t tests. Of the 100, there were 45 in the early and 55 in the late group, with 22/55(40%) operated on day 3. Children with early appendectomy were significantly younger, 7.8 (3.5) versus 9.5 (3.8) years (P = 0.02). Pre-appendectomy, more than 80 per cent of each group had emesis (P = 0.84), but the late group had a 10-fold increase in nasogastric tube use (P = 0.02). The early group tolerated regular diet significantly faster, 2.5 (2.1) versus 4.4 (4.1) days (P = 0.01), and had a significantly shorter hospital stay, 3.5 (2.2) versus 5.6 (4.3) days (P = 0.01). When pain onset to appendectomy is less than three days, the time to return of intestinal function is significantly reduced.

Young children with perforated appendicitis benefit from prompt appendectomy.

BACKGROUND/PURPOSE: To identify factors associated with nonoperative treatment failure in pediatric perforated appendicitis compared to immediate appendectomy. METHODS: After IRB approval, between September 2016 and August 2017, prospective data were recorded for children (age: 1-18 years) with completed appendectomies and pathologist-confirmed perforations. Children were treated according to clinician-designated preference. Nonoperative treatment was considered failed if a nonresolving obstruction developed or any return of symptoms before the planned interval. The median time from pain onset to treatment initiation was 3 days (range: 1-14). Presentation on days 1 or 2 (early) was compared to day 3 or after(late). The nonoperatives were compared to appendectomies stratified by presentation time. Variables were compared by chi-square, Fisher exact or t-tests. Logistic regression evaluated for independence. RESULTS: Of 201 suspected perforations, 176 were included, 101 (57%) immediate appendectomies and 75 (43%) nonoperatives. Of 75, 24 (32%) failed; 6 (25%) in hospital, 18 (75%) after discharge. In 51 (68%), nonoperative treatment succeeded. Significantly younger children failed nonoperative treatment (p = 0.03). Failure was independently associated with treatment initiation within 2.75 days from pain onset (OR: 0.07, 95% CI: 0.57-0.98) (p = 0.010) and lower WBC at presentation (OR: 0.03, 95% CI: 0.81-0.98) (p = 0.014). When compared to immediate appendectomy, nonoperatives had more morbidity. CONCLUSION: Younger children fail nonoperative treatment, perforate rapidly and have a significantly lower WBC, but benefit from immediate appendectomy. LEVEL OF EVIDENCE: Treatment Study Level II.

Safe phlebotomy reduction in stable pediatric liver and spleen injuries.

PURPOSE: Pediatric blunt solid organ injury management based on hemodynamic monitoring rather than grade may safely reduce resource expenditure and improve outcomes. Previously we have reported a retrospectively validated management algorithm for pediatric liver and spleen injuries which monitors hemodynamics without use of routine phlebotomy. We hypothesize that stable blunt pediatric isolated splenic/liver injuries can be managed safely using a protocol reliant on vital signs and not repeat hemoglobin levels. METHODS: A prospective multi-institutional study was performed at three pediatric trauma centers. All pediatric patients from 07/2016-12/2017 diagnosed with liver or splenic injuries were identified. If appropriate for the protocol, only a baseline hemoglobin was obtained unless hemodynamic instability as defined in an age-appropriate fashion was determined by treating physician discretion. Descriptive statistics were conducted. RESULTS: One hundred four patients were identified of which 38 were excluded from the protocol. There was a significant difference in abnormal shock index, pediatric age-adjusted (SIPA) values, hematocrit, and percentage of patients with hemoglobin less than 10 between the excluded and included patients. Of the 66 patients managed on the protocol, four patients had to be removed, two each on day one and day two. Of those four patients, only one required intervention. There were no mortalities. CONCLUSION: A phlebotomy limiting protocol may be a safe option for stable pediatric splenic and liver injuries cared for in a pediatric trauma center with the resources for rapid intervention should the need arise. The differences in groups highlight the importance of utilizing this protocol in the correct patient population. Reduced phlebotomy offers the potential for reduced resource expenditure without any evidence of increased morbidity or mortality. LEVEL OF EVIDENCE: Level IV.