Background Hypovolemic shock reduces oxygen delivery and compromises energy dependent cell volume control. Consequent cell swelling compromises microcirculatory flow, which reducing oxygen exchange further. The importance of this mechanism is highlighted by the effectiveness of cell impermeants in low volume resuscitation (LVR) solutions in acute studies. The objective of this study was to assess impermeants in survival models and compare them to commonly used crystalloid solutions. Methods Adult rats were hemorrhaged to a pressure of 30–35 mm Hg, held there until the plasma lactate reached 10 mM, and given an LVR solution (5–10% blood volume) with saline alone (control), saline with various concentrations of Polyethylene glycol-20k (PEG-20k), hextend or albumin. When lactate again reached 10 mM following LVR, full resuscitation was started with crystalloid and red cells. Rats were either euthanized (acute) or allowed to recover (survival). The LVR time, which is the time from the start of the LVR solution until the start of full resuscitation was measured as was survival and diagnostic labs. In some studies, the capillary oncotic reflection coefficient was determined for PEG-20k to determine its relative impermeant and oncotic effects. Results PEG-20k (10%) significantly increased LVR times relative to saline (8 fold), hextend, and albumin. Lower amounts of PEG-20k (5%) were also effective but less so than 10% doses. PEG-20k maintained normal arterial pressure during the low volume state. Survival of a 180 minute LVR time challenge was 0% in saline controls and 100% in rats given PEG-20k as the LVR solution. Surviving rats had normal labs 24 hours later. PEG-20k had an oncotic reflection coefficient of 0.65, which indicates that the molecule is a hybrid cell impermeant with significant oncotic properties. Conclusions PEG-20k based LVR solutions are highly effective for inducing tolerance to the low volume state and for improving survival.

Hemorrhagic shock leads to cell and tissue swelling and no reflow from compressed capillaries. Cell impermeants, including polyethylene glycol-20,000 (PEG-20k), reverse ischemia-induced cell swelling, extend low-volume resuscitation (LVR) time after shock, and increase tolerance to the low-volume state. The purpose of this study was to explore the mechanisms of action of PEG-20k containing LVR solutions. We hypothesized that PEG-20k acts as both an oncotic agent and an impermeant in the microcirculation, which moves water out of the space and into the capillaries to affect peripheral capillary filling and enhanced perfusion during the low-volume state. Rats were hemorrhaged until arterial lactate reached 9-10 mM/liter. Then, saline-based LVR solutions containing various impermeant materials were administered (10% blood volume). The LVR times for these solutions were determined by measuring the amount of time required for plasma lactate to climb back to 9 to 10 mM after LVR administration (low-volume tolerance). Capillary blood flow was measured by colored microspheres, and blood volume was measured by fluorescein isothiocyanate-labeled albumin dilution. Gluconate (impermeant), albumin (colloid), and PEG-20k (hybrid) increased LVR time over saline by 4-, 3-, and 8-fold, respectively. The combination of impermeant + albumin produced a biologic effect that was similar to PEG-20k alone. Capillary blood flow and plasma volume were decreased after shock with saline LVR but increased with PEG-20k, relative to saline. These data are consistent with the hypothesis that PEG-20k may act by establishing multiple osmotic gradients in the microcirculation to drive cell-to-capillary water transfer during hypovolemic shock.

Objectives The mortality of patients with Clostridum Dificile Associated Disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI) was introduced as an alternative procedure to total colectomy (TC) for CDAD by a single center study. To date, no reproducible results have been published. The objective of this study is to compare these two procedures in a multicentric approach to help the surgeon decide what procedure is best suited for the patient in need. Methods This was a retrospective multicenter study conducted under the sponsorship of the Eastern Association for the Surgery of Trauma (EAST). Demographics, medical history, clinical presentation, APACHE score, and outcomes were collected. We used the Research Electronic Data Capture (REDCap) tool to store the data. Mann-Whitney (continuous data) and Fisher’s Exact (categorical data) were utilized to compare TC with LI. Logistic regression was performed to determine predictors of mortality. A propensity score analysis was done to control for potential confounders and determine adjusted mortality rates by procedure type. Results We collected data from 10 centers of patients that presented with CDAD requiring surgery between July 1of 2010 to July 30 of 2014. Two patients died during the surgical procedure leaving 98 individuals in the study. The overall mortality was 32% and 75% suffered postoperative complications. Median age was 64.5 years, 59% were male. Concerning preoperative patient conditions 54% were on pressors, 47% had renal failure, and 36% suffered respiratory failure. When comparing TC and LI, there was no statistical difference regarding these conditions. Univariate pre-procedure predictors of mortality were age, lactate, timing of operation, vasopressor use, and acute renal failure. There was no statistical difference between the APACHE score of patients undergoing either procedure (TC=22 vs LI= 16). Adjusted mortality (controlled for pre-procedure confounders) was significantly lower in the LI group (17.2% vs. 39.7%, p=0.002). Conclusions This is the first multicenter study comparing TC with LI for the treatment of CDAD. In this study LI carried less mortality than TC. In patients without contraindications, LI should be considered for the surgical treatment of CDAD. Level of evidence prognostic retrospective multi-centric level III

Introduction Polyethylene glycol-20k (PEG-20k) is highly effective for low volume resuscitation (LVR) by increasing tolerance to the low volume state. In our rodent shock model, PEG-20k increased survival and expanded the “golden hour” 16-fold compared to saline. The molecular mechanism is largely attributed to normalizations in cell and tissue fluid shifts after low flow ischemia resulting in efficient microvascular exchange. The objective of this study was to evaluate PEG-20k as a low volume resuscitation solution for hemorrhagic shock in a pre-clinical model. Methods Anesthetized male Yorkshire pigs (30–40 kg) were hemorrhaged to a MAP of 35–40 mmHg. Once lactate reached 7 mM/L, either saline (n = 5) or 10% PEG-20k (n = 5) was rapidly infused at 10% calculated blood volume. The primary outcome was LVR time, defined by the time from LVR administration to the time when lactate again reached 7 mM/L. Other outcomes measured included: MAP, heart rate (HR), cardiac output (CO), mixed venous oxygen saturation (SvO2), splanchnic blood flow, and hemoglobin. Results Relative to saline, PEG-20k given after controlled hemorrhage increased LVR time by 16-fold, a conservative estimate given that the lactate never rose after LVR in the PEG-20k group. Survival was 80% for PEG-20k LVR compared to 0% for the saline controls (P<0.05). PEG-20k also significantly decreased HR after hemorrhage and increased CO, MAP, splanchnic flow, and SvO2. Falling hemoglobin concentrations suggested sizable hemodilution from fluid shifts into the intravascular compartment. Conclusions In a pre-clinical model of controlled hemorrhagic shock, PEG-20k-based LVR solution increased tolerance to the shock state 16-fold compared to saline. PEG-20k is a superior crystalloid for low volume resuscitation that may increase safe transport times in the prehospital setting and find use in hospital emergency departments and operating rooms for patients awaiting volume replacement or normalization of cell, tissue, and compartment fluid volumes.