Effect of increased positive end-expiratory pressure on intracranial pressure and cerebral oxygenation: impact of respiratory mechanics and hypovolemia

Background To evaluate the impact of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) in animals with different respiratory mechanics, baseline ICP and volume status. Methods A total of 50 male adult Bama miniature pigs were involved in four different protocols (n = 20, 12, 12, and 6, respectively). Under the monitoring of ICP, brain tissue oxygen tension and hemodynamical parameters, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O. Measurements were taken in pigs with normal ICP and normovolemia (Series I), or with intracranial hypertension (via inflating intracranial balloon catheter) and normovolemia (Series II), or with intracranial hypertension and hypovolemia (via exsanguination) (Series III). Pigs randomized to the control group received only hydrochloride instillation while the intervention group received additional chest wall strapping. Common carotid arterial blood flow before and after exsanguination at each PEEP level was measured in pigs with intracranial hypertension and chest wall strapping (Series IV). Results ICP was elevated by increased PEEP in both normal ICP and intracranial hypertension conditions in animals with normal blood volume, while resulted in decreased ICP with PEEP increments in animals with hypovolemia. Increasing PEEP resulted in a decrease in brain tissue oxygen tension in both normovolemic and hypovolemic conditions. The impacts of PEEP on hemodynamical parameters, ICP and brain tissue oxygen tension became more evident with increased chest wall elastance. Compare to normovolemic condition, common carotid arterial blood flow was further lowered when PEEP was raised in the condition of hypovolemia. Conclusions The impacts of PEEP on ICP and cerebral oxygenation are determined by both volume status and respiratory mechanics. Potential conditions that may increase chest wall elastance should also be ruled out to avoid the deleterious effects of PEEP.

Effect of Intraoperative Goal-Directed Fluid Management on Tissue Oxygen Tension in Obese Patients: a Randomized Controlled Trial

Background Perioperative subcutaneous tissue oxygen tension (PsqO2) is substantially reduced in obese surgical patients. Goal-directed fluid therapy optimizes cardiac performance and thus tissue perfusion and oxygen delivery. We therefore tested the hypothesis that intra- and postoperative PsqO2 is significantly reduced in obese patients undergoing standard fluid management compared to goal-directed fluid administration. Methods We randomly assigned 60 obese patients (BMI ≥ 30 kg/m2) undergoing laparoscopic bariatric surgery to receive either esophageal Doppler-guided goal-directed fluid management or conventional fluid treatment. Our primary outcome parameter was intra- and postoperative PsqO2 measured with a polarographic electrode in the subcutaneous tissue of the upper arm. A random effects linear regression model was used to analyze the effect of intervention. Results Overall, mean (± SD) PsqO2 was significantly higher in obese patients receiving goal-directed therapy compared to conventional fluid therapy (65.8 ± 28.0 mmHg vs. 53.7 ± 21.7, respectively; repeated measures design adjusted difference: 13.0 mmHg [95% CI 2.3 to 23.7; p = 0.017]). No effect was seen intraoperatively (69.6 ± 27.9 mmHg vs. 61.4 ± 28.8, difference: 9.7 mmHg [95% CI -3.8 to 23.2; p = 0.160]); however, goal-directed fluid management improved PsqO2 in the early postoperative phase (63.1 ± 27.9 mmHg vs. 48.4 ± 12.5, difference: 14.5 mmHg [95% CI 4.1 to 24.9; p = 0.006]). Intraoperative fluid requirements did not differ between the two groups. Conclusions Goal-directed fluid therapy improved subcutaneous tissue oxygenation in obese patients. This effect was more pronounced in the early postoperative period. Clinical Trial Number and Registry The study was registered at ClinicalTrials.gov (NCT 01052519).

Mild hypercapnia improves brain tissue oxygen tension but not diffusion limitation in asphyxial cardiac arrest: an experimental study in pigs

Background We sought to evaluate the effect of mild hypercapnia on brain tissue oxygen tension (Pbto2) and diffusion limitation (impaired ability of oxygen extraction) in a porcine post asphyxial cardiac arrest model. Methods In 16 Bama pigs, asphyxial cardiac arrest was induced by endotracheal tube clamping and remained untreated for another 4 min. After return of spontaneous circulation (ROSC), animals were randomly assigned to mild hypercapnia (end-tidal carbon dioxide (EtCO2): 45 ~ 50 mmHg) and normocapnia (EtCO2: 35 ~ 40 mmHg) groups for 12 h. Intracranial pressure (ICP), Pbto2, and brain tissue temperature were invasively measured by multimodality monitors. Blood gas analysis, neuron specific enolase (NSE), and S100β were tested at baseline, ROSC 1 h, 6 h, and 12 h. Generalized mixed model with a compound symmetry covariance matrix was used to compare the time-variables of the two groups. Results Twelve (75%) pigs had ROSC and 11 pigs survived for the study period, with 6 pigs in mild hypercapnia group and 5 in the normocapnia group. The mean EtCO2 in the mild hypercapnia was significantly higher than normocapnia group (48 vs 38 mmHg, p < 0.001). Compared with normocapnia, mild hypercapnia group had higher Pbto2 (p < 0.001), slightly higher mean arterial pressure (p = 0.012) and ICP (p = 0.009). There were no differences in cerebral perfusion pressure (p = 0.106), gradient of partial pressure of jugular venous bulb oxygen (Pjvo2) and Pbto2 (p = 0.262), difference of partial pressure of jugular venous CO2 and arterial CO2 (p = 0.546), cardiac output (p = 0.712), NSE (p = 0.822), and S100β (p = 0.759) between the two groups. Conclusions Short term mild hypercapnia post-resuscitation could improve Pbto2. However, no corresponding improvements in the gradient of Pjvo2 to Pbto2 and biomarkers of neurological recovery were observed in the porcine asphyxial cardiac arrest model.

4511 Bio-Compatible Implantable Oxygen Sensor Technology with Real-Time Monitoring of Surgical Flaps and Reimplantation

OBJECTIVES/GOALS: Current surgical flap and replantation monitoring techniques have limitations in detecting the pathologic state, calibration and cost-to-patient issues. Our hypothesis is that novel implantable oxygen sensors can provide a more efficient, accurate, and reliable monitoring of tissue oxygenation. METHODS/STUDY POPULATION: Experimental sensors were used with an exogenous remote used as a reader once implanted (Fig. 1) A rat tissue perfusion model with three regions of an SIEA flap as well as into adjacent control sites was made (Tip, Middle, and Base) Blood flow was greatest at the base, diminishing towards the Tip, thus creating a perfusion gradient. Changes in tissue oxygen tension PO2 were estimated by the steady-state fluorescence of the optical sensors using an IVIS imaging system. The sensors were used to collect data from days 0, 3, and 7 as a reading of Tissue Oxygen Tension (TOT) with ANOVA used to assess for statistical significance in blood oxygen data with respect to relative perfusion status. RESULTS/ANTICIPATED RESULTS: Inspired FiO2 was decreased from 100% to 12% with a corresponding change in the TOT readings from all sensors. (Fig. 2) The tip portion of the flap demonstrated the most profound detection of tissue necrosis, with the middle demonstrating the second most necrosis and the base demonstrating the least with correlating TOT sensor readings. (Fig. 3) Acute vascular compromise of the feeding blood vessels in the pedicle was immediately detected within 70 seconds (*p<0.05). (Fig. 4) DISCUSSION/SIGNIFICANCE OF IMPACT: This study introduces and validates a recent technique to monitor acute vascular occlusion, flap viability, and necrosis in the immediate postoperative period in a validated rodent model. Future directions of this novel technology will aim to reproduce these findings in clinical feasibility studies.