Peritoneal Resuscitation Research Articles

Therapeutic interventions using the peritoneal and coelomic cavity in dogs, cats, and exotic pets.

To provide a video tutorial describing intraperitoneal (IP) and intracoelomic (IC) therapeutics (IP/IC fluid therapy, euthanasia, direct peritoneal resuscitation). Dogs, cats, and exotic pets. Peritoneal and coelomic centesis allows for delivery of fluids or to perform euthanasia. The peritoneal and coelomic membranes contain a vast network of capillaries and lymphatics that allow absorption of fluids and blood products. Needles are inserted aseptically IP or IC at species-specific locations to avoid iatrogenic damage. In mammals, the needle is inserted in a periumbilical location at a 1- to 2-cm radius from the umbilicus, while the needle is inserted into the ventral inguinal fossa in chelonians and lateroventrally in lizards and snakes. Direct peritoneal resuscitation is a human technique in which a dextrose/electrolyte solution infused IP reduces ischemia-reperfusion injury, edema, and tissue necrosis to improve mortality in patients with diseases like shock and sepsis or who require acute abdominal surgery. Isotonic crystalloids are given IP/IC at 10- to 20-mL/kg doses (smaller volumes in reptiles) and blood products at standard calculated doses. Sodium pentobarbital without phenytoin (3 mL/4.5 kg) is used for IP/IC euthanasia. Being aware of multiple routes for fluid and blood product administration allows treatment in animals for which intravenous or intraosseous catheterization is undesirable or impossible. While intravenous or intraosseous routes are always preferred, especially for resuscitation, familiarity with locations for IP/IC fluid and euthanasia is useful. Techniques like direct peritoneal resuscitation are not currently used in animals but might be translated to veterinary cases in the future.

Phase I clinical trial of the feasibility and safety of direct peritoneal resuscitation in liver transplantation

BackgroundDirect peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). MethodsLT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8–24 ​h depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity ​+ ​renal dysfunction, control-2) were analyzed. ResultsFifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 ​% of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. ConclusionDPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.

Direct peritoneal resuscitation in a patient with gastrointestinal tuberculosis with an open abdomen

Rationale/objectivesThis case report aims to illustrate the methodology involved in the management of a patient with gastrointestinal tuberculosis with an open abdomen with direct peritoneal resuscitation. We present a 49-year-old malnourished male, in septic shock, who presented with mechanical intestinal obstruction from gastrointestinal tuberculosis (GITB) and required delayed abdominal closure. Direct peritoneal resuscitation (DPR) was employed as an adjunct to shorten the interval to closure by reducing organ edema and inflammatory cytokine levels. MethodsThis is a case report describing the procedure of direct peritoneal resuscitation and its use in non-trauma related surgeries requiring delayed abdominal closure. ResultsThe patient recovered well from the surgery with the abdomen closed after nine days from the first procedure. ConclusionDirect peritoneal resuscitation is a viable adjunct in patients requiring delayed abdominal closure.

An Unusual Presentation of Crohn’s Disease and Novel Use of Direct Peritoneal Resuscitation

Crohn’s disease is an inflammatory bowel disease characterized by transmural inflammation, with the majority of patients having small bowel involvement, usually the distal ileum. Typical manifestations include a prolonged course of abdominal pain, diarrhea, fatigue, and weight loss. We report a case of a 21-year-old male who presented with an acute abdomen and was in profound shock resulting in cardiac arrest. The patient underwent damage control, exploratory laparotomy complicated by acute hypoxic respiratory failure requiring veno-venous extracorporeal membrane oxygenation and the novel use of direct peritoneal resuscitation in the setting of an acute abdomen with an uncontrolled enterotomy and bowel spillage. Our case report illustrates the importance of prompt surgical intervention and critical care with the application of novel surgical techniques to minimize mortality in an unusual presentation of Chron’s disease.

Effect of Plasma Resuscitation with Adjunctive Peritoneal Resuscitation on Hepatic Blood Flow and End-Organ Damage after Hemorrhagic Shock.

Intestinal injury from resuscitated hemorrhagic shock (HS) disrupts intestinal microvascular flow and causes enterocyte apoptosis, intestinal barrier breakdown, and injury to multiple organs. Fresh frozen plasma (FFP) resuscitation or directed peritoneal (DPR) resuscitation protect endothelial glycocalyx, improve intestinal blood flow, and alleviate intestinal injury. We postulated that FFP plus DPR might improve effective hepatic blood flow (EHBF) and prevent associated organ injury (liver, heart). Anesthetized Sprague-Dawley rats underwent HS (40% mean arterial pressure, 60 minutes) and were randomly assigned to groups (n = 8 per group): Sham; crystalloid resuscitation (CR; shed blood + 2 volumes CR); DPR (intraperitoneal 2.5% peritoneal dialysis fluid); FFP (shed blood + 1 vol IV FFP); FFP + DPR. EHBF was measured at postresuscitation timepoints. Organ injury was evaluated by serum ELISA (fatty acid-binding protein [FABP]-1 [liver], FABP-3 [heart], Troponin-I [heart], and Troponin-C [heart]) and hematoxylin and eosin. Differences were evaluated by 1-way ANOVA and 2-way repeated-measures ANOVA. CR resuscitation alone did not sustain EHBF. FFP resuscitation restored EHBF after resuscitation (2 hours, 3 hours, and 4 hours). DPR resuscitation restored EHBF throughout the postresuscitation period but failed to restore serum FABP-1 VS other groups. Combination FFP + DPR rapidly and sustainably restored EHBF and decreased organ injury. CR and DPR alone had elevated organ injury (FABP-1 [hepatocyte], FABP-3 [cardiac], and Troponin-I/C), whereas FFP or FFP + DPR demonstrated reduced injury at 4 hours after resuscitation. HS decreased EHBF, hepatocyte injury, and cardiac injury as evidenced by serology. FFP resuscitation improved EHBF and decreased organ damage. Although DPR resuscitation resulted in sustained EHBF, this alone failed to decrease hepatocyte or cardiac injury. Combination therapy with DPR and FFP may be a novel method to improve intestinal and hepatic blood flow and decrease organ injury after HS/resuscitation.

Direct Peritoneal Resuscitation (DPR) Improves Acute Physiology and Chronic Health Evaluation (APACHE) IV and Acute Physiology Score When Used in Damage Control Laparotomies: Prospective Cohort Study on 37 Patients.

Using direct peritoneal resuscitation (DPR) as an adjunct when managing patients undergoing damage control laparotomy (DCL) shows promising results. We report our initial experience in utilizing DPR when managing patients who underwent DCL for emergent surgery at the index operation. We prospectively collected data on 37 patients between August 2020 to October 2021 who underwent DCL with open abdomens after the index operation and utilized DPR. DPR was performed using peritoneal lavage with DIANEAL PD-2-D 2.5% Ca 3.5 mEq/L at a rate of 400ml/hour. Patients' physiological scores and clinical outcomes were evaluated. 86% required DCL and DPR due to septic abdomen/bowel ischemia. The median (interquartile range [IQR]) age was 62 years (53-70); 62% were male, and median (IQR) body mass index was 30.0kg/m2 (25.5-38.4). On DPR initiation, median (IQR) APACHE-IV score was 48 (33-64) and median (IQR) Acute Physiology Score (APS) was 31 (18-54). After initiation, median (IQR) APACHE-IV score and median (IQR) APS were 39 (21-62) and 19 (11-56), respectively, and both showed significant improvement in survivors (p<0.05). Median (IQR) DPR duration was four days (2-8) and primary abdominal closure was achieved in 30 patients (81%). There were eight mortalities (21.6%) within 30 days postoperatively, of which seven were within 3-24 days due to uncontrolled sepsis/multiple organ failure. The most frequent complication was surgical-site infection recorded in 12 patients (32%). Twenty-four patients (67%) were discharged home/transferred to a rehab center/nursing home. DPR application showed significant improvement of APACHE-IV score and APS in patients with peritonitis/septic abdomen.

Effects and Mechanisms of Peritoneal Resuscitation on Acute Kidney Injury After Severe Burns in Rats.

Acute kidney injury (AKI) is a common complication in severe burn patients with poor prognosis and high mortality. Reduced kidney perfusion induced by the decreased effective circulating blood volume after severe burn is a common cause of AKI. Routine intravenous resuscitation (IR) is difficult or delayed in extreme conditions such as war and disaster sites. Peritoneal resuscitation (PR) is a simple, rapid resuscitation strategy via a puncture in the abdominal wall. This study investigated whether PR is a validated resuscitation strategy for AKI after severe burns in rats and explored its mechanisms. Eighty Sprague-Dawley rats were randomized into four groups: (1) sham group; (2) IR group, which was characterized by the full thickness burn of 50% of the total body surface area received IR immediately post-injury; (3) early PR group, in which rats with the same burn model received PR immediately post-injury; and (4) delayed resuscitation (DR) group, in which rats with the same burn model received no resuscitation within 3-hour post-injury. PR and DR groups animals received IR after 3-hour post-injury. The survival rate, mean arterial pressure, renal histopathology, renal function, indicators of renal injury, and renal hypoxia-inducible factor-1α and NADPH oxidase 4 (NOX4) proteins of rats were measured at 3 h, 12 h, and 24 h post-injury. Compared with rats in the DR group, rats in the PR group had a significantly improved survival rate (100% vs. 58.3% at 24 h, P = 0.0087), an increased mean arterial pressure (92.6 ± 6.6 vs. 65.3 ± 10.7, 85.1 ± 5.7 vs. 61.1 ± 6.9, 90.1 ± 8.7 vs. 74.9 ± 7.4 mmHg, at 3 h, 12 h, and 24 h, P < 0.01), a reduced renal water content rate (51.6% ± 5.0% vs. 70.1% ± 6.8%, 57.6% ± 7.7% vs. 69.5% ± 8.7%, at 12 h and 24 h, P < 0.01), attenuated histopathological damage, reduced serum creatinine expression (36.36 ± 4.27 vs. 49.98 ± 2.42, 52.29 ± 4.31 vs. 71.32 ± 5.2, 45.25 ± 2.55 vs. 81.15 ± 6.44 μmol/L, at 3 h, 12 h, and 24 h, P < 0.01) and BUN expression (7.62 ± 0.30 vs. 10.80 ± 0.58, 8.61 ± 0.32 vs. 28.58 ± 1.99, 8.09 ± 0.99 vs. 20.95 ± 1.02 mmol/L, at 3 h, 12 h, and 24 h, P < 0.01), increased kidney injury markers neutrophil gelatinase-associated lipocalin expression (95.09 ± 7.02 vs. 101.75 ± 6.23, 146.77 ± 11.54 vs. 190.03 ± 9.87, 112.79 ± 15.8 vs. 194.43 ± 11.47 ng/mL, at 3 h, 12 h, and 24 h, P < 0.01) and cystatin C expression (0.185 ± 0.006 vs. 0.197 ± 0.006, 0.345 ± 0.036 vs. 0.382 ± 0.013, 0.297 ± 0.012 vs. 0.371 ± 0.028 ng/mL, at 3 h, 12 h, and 24 h, P < 0.01), and reduced renal hypoxia-inducible factor-1α and NADPH oxidase 4 protein expression (P < 0.01). There was no significant difference between rats in the PR group and the IR group in the above indicators. Early PR could protect severe burn injury rats from AKI. It may be an alternative resuscitation strategy in severe burn injury when IR cannot be achieved.

Direct Peritoneal Resuscitation in Trauma Patients Results in Similar Rates of Intra-Abdominal Complications.

Background: Trauma patients undergoing damage control surgery (DCS) have a propensity for complicated abdominal closures and intra-abdominal complications. Studies show that management of open abdomens with direct peritoneal resuscitation (DPR) reduces intra-abdominal complications and accelerates abdominal closure. This novel study compares intra-abdominal complication rates and the effect of DPR initiation in patients who received DPR and those who did not. Patients and Methods: A retrospective chart review was performed on 120 patients who underwent DCS. Fifty patients were identified as DCS with DPR, and matched to 70 controls by gender, race, age, body mass index (BMI), past medical history, mechanism of trauma, and injury severity score. Results: The two groups of patients, those without DPR (-DPR) and those with DPR (+DPR), were similar in their characteristics. The +DPR group was more likely to have a mesh closure than the -DPR (14% and 3%; p = 0.022). The +DPR group took longer to have a final closure (3.5 ± 2.6 days vs. 2.5 ± 1.8; p = 0.020). Infection complications and mechanical failure of the closure technique were similar among the two groups. Timing of DPR initiation had no effect on closure type but did statistically increase the number of days to closure (initiation at first operation 2.8 ± 1.8 days vs. initiation at subsequent operations 6.0 ± 3.3 days; p ≤ 0.001). Conclusions: The use of DPR did not result in different outcomes in trauma patients. Therefore, traditional resuscitative measures for DCS may not be inferior to DCS with DPR. When choosing to use DPR, initiating it at the first operation could reduce the number of days to closure.

The role of direct peritoneal resuscitation in the treatment of hemorrhagic shock after trauma and in emergency acute care surgery: a systematic review.

Direct peritoneal resuscitation (DPR) has been used to help preserve microcirculation by reversing vasoconstriction and hypoperfusion associated with the pathophysiological process of shock, which can occur despite appropriate intravenous resuscitation. This approach depends on infusing a hyperosmolar solution intraperitoneally via a percutaneous catheter with the tip ending near the pelvis or the root of the mesentery. The abdomen is usually left open with a negative pressure abdominal dressing to continuously evacuate the infused dialysate. Hypertonicity of the solution triggers visceral vasodilation to help maintain blood flow, even during shock, and is also associated with reduced local inflammatory cytokines and other mediators, preservation of endothelial cell function, and mitigation of organ edema and necrosis. It also has a direct effect on liver perfusion and edema, more rapidly corrects electrolyte abnormalities compared to intravenous resuscitation alone, and may requireless intravenous fluid to stabilize blood pressure, all of which shortens the time required to close patients' abdomen. An online query using the search term "direct peritoneal resuscitation" was carried out in PubMed, MEDLINE and SciELO, limited to publications indexed from January 2014 to June 2020. Of the 20 articles returned, full text was able to be obtained for 19. A manual review of included articles' references was resulted in the addition of 1 article, for a total of 20 included articles. The 20 articles were comprised of 15 animal studies, 4 clinical studies,and 1 expert opinion. The benefits include both local and possibly systemic effects on perfusion, hypoxia, acidosis, and inflammation, and are associated with improved outcomes and reduced complications. DPR shows promise in patients with hemorrhagic shock, septic shock, and other conditions resulting in an open abdomen after damage control laparotomy.

Renal Outcomes and Safety Profile of Direct Peritoneal Resuscitation (DPR)

Renal Outcomes and Safety Profile of Direct Peritoneal Resuscitation (DPR)

A Review of "Direct Peritoneal Resuscitation Accelerates Primary Abdominal Wall Closure After Damage Control Surgery" (2010).

A Review of "Direct Peritoneal Resuscitation Accelerates Primary Abdominal Wall Closure After Damage Control Surgery" (2010).

Plasma resuscitation with adjunctive peritoneal resuscitation reduces ischemia-induced intestinal barrier breakdown following hemorrhagic shock.

Hemorrhagic shock (HS) and resuscitation (RES) cause ischemia-induced intestinal permeability due to intestinal barrier breakdown, damage to the endothelium, and tight junction (TJ) complex disruption between enterocytes. The effect of hemostatic RES with blood products on this phenomenon is unknown. Previously, we showed that fresh frozen plasma (FFP) RES, with or without directed peritoneal resuscitation (DPR) improved blood flow and alleviated organ injury and enterocyte damage following HS/RES. We hypothesized that FFP might decrease TJ injury and attenuate ischemia-induced intestinal permeability following HS/RES. Sprague-Dawley rats were randomly assigned to groups (n = 8): sham; crystalloid resuscitation (CR) (HS of 40% mean arterial pressure for 60 minutes) and CR (shed blood plus two volumes of CR); CR and DPR (intraperitoneal 2.5% peritoneal dialysis fluid); FFP (shed blood plus one volume of FFP); and FFP and DPR (intraperitoneal dialysis fluid plus two volumes of FFP). Fluorescein isothiocyanate-dextran (molecular weight, 4 kDa; FD4) was instilled into the gastrointestinal tract before hemorrhage; FD4 was measured by UV spectrometry at various time points. Plasma syndecan-1 and ileum tissue TJ proteins were measured using enzyme-linked immunosorbent assay. Immunofluorescence was used to visualize claudin-4 concentrations at 4 hours following HS/RES. Following HS, FFP attenuated FD4 leak across the intestine at all time points compared with CR and DPR alone. This response was significantly improved with the adjunctive DPR at 3 and 4 hours post-RES (p < 0.05). Resuscitation with FFP-DPR increased intestinal tissue concentrations of TJ proteins and decreased plasma syndecan-1. Immunofluorescence demonstrated decreased mobilization of claudin-4 in both FFP and FFP-DPR groups. Fresh frozen plasma-based RES improves intestinal TJ and endothelial integrity. The addition of DPR can further stabilize TJs and attenuate intestinal permeability. Combination therapy with DPR and FFP to mitigate intestinal barrier breakdown following shock could be a novel method of reducing ischemia-induced intestinal permeability and systemic inflammation after trauma. Prognostic/Epidemiologic, Level III.

Plasma resuscitation with adjunctive peritoneal resuscitation reduces ischemic intestinal injury following hemorrhagic shock.

Impaired intestinal microvascular perfusion following resuscitated hemorrhagic shock (HS) leads to ischemia-reperfusion injury, microvascular dysfunction, and intestinal epithelial injury, which contribute to the development of multiple organ dysfunction syndrome in some trauma patients. Restoration of central hemodynamics with traditional methods alone often fails to fully restore microvascular perfusion and does not protect against ischemia-reperfusion injury. We hypothesized that resuscitation (RES) with fresh frozen plasma (FFP) alone or combined with direct peritoneal resuscitation (DPR) with 2.5% Delflex solution might improve blood flow and decrease intestinal injury compared with conventional RES or RES with DPR alone. Sprague-Dawley rats underwent HS (40% mean arterial pressure) for 60 minutes and were randomly assigned to a RES group (n = 8): sham, HS-crystalloid resuscitation (CR) (shed blood + two volumes CR), HS-CR-DPR (intraperitoneal 2.5% peritoneal dialysis fluid), HS-FFP (shed blood + two volumes FFP), and HS-DPR-FFP (intraperitoneal dialysis fluid + two volumes FFP). Laser Doppler flowmeter evaluation of the ileum, serum samples for fatty acid binding protein enzyme-linked immunosorbent assay, and hematoxylin and eosin (H&E) staining were used to assess intestinal injury and blood flow. p Values of <0.05 were considered significant. Following HS, the addition of DPR to either RES modality improved intestinal blood flow. Four hours after resuscitated HS, FABP-2 (intestinal) and FABP-6 (ileal) were elevated in the CR group but reduced in the FFP and DPR groups. The H&E staining demonstrated disrupted intestinal villi in the FFP and CR groups, most significantly in the CR group. Combination therapy with FFP and DPR demonstrated negligible cellular injury in H&E graded samples and a significant reduction in fatty acid binding protein levels. Hemorrhagic shock leads to ischemic-reperfusion injury of the intestine, and both FFP and DPR alone attenuated intestinal damage; combination FFP-DPR therapy alleviated most signs of organ injury. Resuscitation with FFP-DPR to restore intestinal blood flow following shock could be an essential method of reducing morbidity and mortality after trauma.

Direct Peritoneal Resuscitation Improves Survival in a Murine Model of Combined Hemorrhage and Burn Injury.

Combined burn injury and hemorrhagic shock are a common cause of injury in wounded warfighters. Current protocols for resuscitation for isolated burn injury and isolated hemorrhagic shock are well defined, but the optimal strategy for combined injury is not fully established. Direct peritoneal resuscitation (DPR) has been shown to improve survival in rats after hemorrhagic shock, but its role in a combined burn/hemorrhage injury is unknown. We hypothesized that DPR would improve survival in mice subjected to combined burn injury and hemorrhage. Male C57/BL6J mice aged 8weeks were subjected to a 7-second 30% total body surface area scald in a 90°C water bath. Following the scald, mice received DPR with 1.5mL normal saline or 1.5mL peritoneal dialysis solution (Delflex). Control mice received no peritoneal solution. Mice underwent a controlled hemorrhage shock via femoral artery cannulation to a systolic blood pressure of 25mmHg for 30minutes. Mice were then resuscitated to a target blood pressure with either lactated Ringer's (LR) or a 1:1 ratio of packed red blood cells (pRBCs) and fresh frozen plasma (FFP). Mice were observed for 24 hours following injury. Median survival time for mice with no DPR was 1.47hours in combination with intravascular LR resuscitation and 2.08 hours with 1:1 pRBC:FFP. Median survival time significantly improved with the addition of intraperitoneal normal saline or Delflex. Mice that received DPR followed by 1:1 pRBC:FFP required less intravascular volume than mice that received DPR with LR, pRBC:FFP alone, and LR alone. Intraperitoneal Delflex was associated with higher levels of tumor necrosis factor alpha and macrophage inflammatory protein 1 alpha and lower levels of interleukin 10 and intestinal fatty acid binding protein. Intraperitoneal normal saline resulted in less lung injury 1hour postresuscitation, but increased to similar severity of Delflex at 4hours. After a combined burn injury and hemorrhage, DPR leads to increased survival in mice. Survival was similar with the use of normal saline or Delflex. DPR with normal saline reduced the inflammatory response seen with Delflex and delayed the progression of acute lung injury. DPR may be a valuable strategy in the treatment of patients with combined burn injury and hemorrhage.

Effect of peritoneal dialysis solution with different pyruvate concentrations on intestinal injury.

To investigate the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (Pyr-PDS) of different concentrations combined with intravenous resuscitation on acid–base imbalance and intestinal ischemia reperfusion injury in rats with hemorrhagic shock. Sixty rats were randomly assigned to group SHAM, group intravenous resuscitation, and four direct peritoneal resuscitation groups combined with intravenous resuscitation: group NS, LA, PY1, and PY2, that is, normal saline, lactate-PDS (Lac-PDS), lower concentration Pyr-PDS (Pyr-PDS1), and higher concentration Pyr-PDS (Pyr-PDS2), respectively. Two hours after hemorrhagic shock and resuscitation, the pH, oxygen partial pressure, carbon dioxide partial pressure (PCO2), base excess, and bicarbonate ion concentration (HCO3−) of the arterial blood were measured. The intestinal mucosal damage index and intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor-α, interleukin-6, zonula occludens-1, claudin-1, and occludin levels in intestinal issues were detected. Two hours after resuscitation, group PY2 had higher mean arterial pressure, pH, oxygen partial pressure, and base excess and lower PCO2of arterial blood than group PY1 ( P &lt; 0.05). Tumor necrosis factor-α and interleukin-6 levels in group PY2 were significantly lower than those in group PY1 ( P &lt; 0.05). Zonula occludens-1, claudin-1, and occludin expression levels were significantly higher in group PY2 than in group PY1 ( P &lt; 0.05). Direct peritoneal resuscitation with Pyr-PDS2 combined with intravenous resuscitation enhanced the hemodynamics, improved the acid–base balance, and alleviated intestinal ischemia reperfusion injury from hemorrhagic shock and resuscitation in rats. The mechanisms might include correction of acidosis, inhibition of inflammatory response, enhancement of systemic immune status, regulation of intestinal epithelial permeability, and maintenance of intestinal mucosal barrier function.Impact statementHemorrhagic shock is a life-threatening condition after trauma or during surgery. Acid–base imbalance and intestinal ischemia reperfusion injury are two significant causes in the pathogenetic process and multiple organ dysfunction. As a result, it is urgent and necessary to find an effective method of resuscitation in order to reverse the acid–base imbalance and protect organ function. This current study confirmed the protection against hypoxic acidosis and intestinal ischemia reperfusion injury by peritoneal resuscitation with pyruvate combined with intravenous resuscitation in rats with hemorrhagic shock. And the peritoneal dialysis solution with pyruvate of high concentration plays a crucial role in the process. It provided a new idea and possible direction of fluid resuscitation for alleviating organ injuries, protecting organ functions, and improving clinical prognosis after hemorrhagic shock and resuscitation.

Direct Peritoneal Resuscitation with Pyruvate Protects the Spinal Cord and Induces Autophagy via Regulating PHD2 in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury.

Direct peritoneal resuscitation with pyruvate (Pyr-PDS) has emerged as an interesting candidate to alleviate injury in diverse organs, while the potential mechanism has yet to be fully elucidated. To explore the effect of autophagy in the spinal cord ischemia-reperfusion (SCIR) injury and the underlying mechanism, we established a model of SCIR in vivo and in vitro. In vivo, male SD rats underwent aortic occlusion for 60 min and then followed by intraperitoneally infused with 20 mL of pyruvate or normal saline for 30 min, and the spinal cords were removed for analysis after 48 h of reperfusion. The functional and morphological results showed that Pyr-PDS alleviated SCIR injury; meanwhile, the expression of autophagy-related genes and transmission electron microscopy displayed autophagy was activated by SCIR injury, and Pyr-PDS treatment could further upregulate the degree of autophagy which plays a protective part in the SCIR injury, while there is no significant difference after treatment with saline. In addition, SCIR injury inhibited expression of PHD2, which results to activate its downstream HIF-1α/BNIP3 pathway to promote autophagy. In the Pyr-PDS, the results revealed PHD2 was further inhibited compared to the SCIR group, which could further activate the HIF-1α/BNIP3 signaling pathway. Additionally, oxygen-glucose deprivation and reoxygenation were applied to SH-SY5Y cells to mimic anoxic conditions in vitro, and the expression of autophagy-related genes, PHD2, and its downstream HIF-1α/BNIP3 pathway showed the same trend as the results in vivo. Besides, IOX2, a specific inhibitor of PHD2 was also treated to SH-SY5Y cells during reoxygenation, in which the result is as same as the pyruvate group. Then, we observed the expression of autophagy-related genes and the HIF-1α signal pathway in the process of reoxygenation; the results showed that as the reoxygenation goes, the expression of the HIF-1α signal pathway and degree of autophagy came to decrease gradually, while treated with pyruvate could maintain autophagy high and stable through keeping PHD2 at a lower level during reoxygenation, and the latter was observed downregulated during reoxygenation process from 0 to 24 hours in a time-effect way. The above results indicated that direct peritoneal resuscitation with pyruvate showed effective protection to ischemia-reperfusion of the spinal cord through activating autophagy via acting on PHD2 and its downstream HIF-1α/BNIP3 pathway.

Pyruvate Protects Against Intestinal Injury by Inhibiting the JAK/STAT Signaling Pathway in Rats With Hemorrhagic Shock

BackgroundThis study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. Materials and MethodsSixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). ResultsAt 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. ConclusionsThe protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.

Direct Peritoneal Resuscitation: A Novel Adjunct to Damage Control Laparotomy.

Direct peritoneal resuscitation is a validated resuscitation strategy for patients undergoing damage control surgery for hemorrhage, sepsis, or abdominal compartment syndrome with open abdomen and planned reexploration after a period of resuscitation in the intensive care unit. Direct peritoneal resuscitation can decrease visceral edema, normalize body water ratios, accelerate primary abdominal wall closure after damage control surgery, and prevent complications associated with open abdomen. This review article describes the physiological benefits of direct peritoneal resuscitation, how this technique fits within management priorities for the patient in shock, and procedural components in the care of open abdomen surgical patients receiving direct peritoneal resuscitation. Strategies for successful implementation of a novel multidisciplinary intervention in critical care practice are explored.

Effect of pyruvate peritoneal resuscitation on JAK/STAT signaling pathway in intestinal tissues of rats with hemorrhagic shock

Objective To evaluate the effect of pyruvate peritoneal resuscitation on Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway in intestinal tissues of rats with hemorrhagic shock. Methods Twenty-four healthy male Sprague-Dawley rats, weighing 200-300 g, were divided into 3 groups (n=8 each) using a random number table method: sham operation group (S group), intravenous resuscitation group (VR group), and peritoneal resuscitation with pyruvate group (PY group). Hemorrhagic shock was induced by blood-letting and infusing blood withdrawn with mean arterial pressure reduced to 30-40 mmHg for 60 min in pentobarbital-anesthetized rats.Hemorrhagic shock was resuscitated with autologous blood and normal saline 2 times the volume of blood withdrawn at the end of hemorrhagic shock in group VR.Pyruvate was intraperitoneally infused for 30 min using a micro-perfusion pump simultaneously with the intravenous resuscitation in group PY.The animals were sacrificed at 2 h after resuscitation, and intestinal tissues were obtained for determination of malondialdehyde (MDA) content (by thiobarbituric acid method), superoxide dismutase (SOD) activity (using xanthine oxidase method), myeloperoxidase (MPO) activity (using chemical colorimetry), and expression of phosphorylated STAT3 (p-STAT3), phosphorylated JAK2 (p-JAK2) and caspase-3 expression (by Western blot). Results Compared with group S, the MDA content and MPO activity were significantly increased, the SOD activity was decreased, and the expression of p-STAT3, p-JAK2 and caspase-3 was up-regulated in the other two groups (P<0.05). Compared with group VR, the MDA content and MPO activity were significantly decreased, the SOD activity was increased, and the expression of p-STAT3, p-JAK2 and caspase-3 was down-regulated in group PY (P<0.05). Conclusion The mechanism by which peritoneal resuscitation with pyruvate mitigates intestinal damage may be related to inhibiting activation of JAK/STAT signaling pathway in the rats with hemorrhagic shock. Key words: Pyruvic acid; Resuscitation; Shock, hemorrhagic; Intestines; Janus kinases; STAT transcription factors

Direct Peritoneal Resuscitation Reduces Lung Injury and Caspase 8 Activity in Brain Death*

Background: Acute brain death (ABD) is associated with inflammation and lung injury. Direct peritoneal resuscitation (DPR) improves blood flow to the vital organs after ABD. DPR reduces lung injury, but the mechanism for this is unknown. Methods: Male Sprague-Dawley rats were randomized to five groups (n = 8/group): (1) Sham (no ABD); (2) Targeted intravenous fluid (TIVF) (ABD plus enough IVF to maintain a MAP of 80 mmHg) at 2 hours post-resuscitation (RES); (3) ABD + TIVF + DPR (TIVF and 30 cc intraperitoneal 2.5% Delflex) at 2 hours post-RES; (4) ABD + TIVF at 4 hours post-RES; and (5) ABD + TIVF + DPR at 4 hours post-RES. Messenger RNA (mRNA) levels were measured using Qiagen qRT PCR. Protein levels were assessed using quantitative ELISAs and the Luminex MagPix system. Results: Use of DPR caused 5.8-fold downregulation of mRNA expression for TNF-α and 2.7-fold decrease for the TNF receptor compared to TIVF alone. Caspase 8 mRNA was also downregulated. Protein levels for TNF-α, TNF receptor, caspase 8, NFκB, and NFκB inhibitor kinase, which promotes dissociation of NFκB inhibitor, were reduced by DPR. Cell death markers M30 and M65 were also decreased with DPR. Conclusions: Use of DPR caused changes in the expression of multiple mRNAs and proteins in the caspase 8 apoptotic pathway. These data represent a mechanism through which DPR exerts its beneficial effects within the lung tissue.