Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia-reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia.

BACKGROUND: Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking. METHODS: In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women. RESULTS: The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09). CONCLUSIONS: In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. METHODS: In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. RESULTS: In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. CONCLUSIONS: This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).

Is cerebral perfusion maintained during full and partial resuscitative endovascular balloon occlusion of the aorta in hemorrhagic shock conditions?

BACKGROUND: Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is a technology that occludes aortic flow and allows for controlled deflation and restoration of varying distal perfusion. Carotid flow rates (CFRs) during partial deflation are unknown. Our aim was to measure CFR with the different pREBOA balloon volumes and correlate those to the proximal mean arterial pressure (PMAP) and a handheld pressure monitoring device (COMPASS; Mirador Biomedical, Seattle, WA). METHODS: Ten swine underwent a hemorrhagic injury model with carotid and iliac arterial pressures monitored via arterial lines. Carotid and aortic flow rates were monitored with Doppler flow probes. A COMPASS was placed to monitor proximal pressure. The pREBOA was inflated for 15 minutes then partially deflated for an aortic flow rate of 0.7 L/min for 45 minutes. It was then completely deflated. Proximal mean arterial pressures and CFR were measured, and correlation was evaluated. Correlation between CRF and COMPASS measurements was evaluated. RESULTS: Carotid flow rate increased 240% with full inflation. Carotid flow rate was maintained at 100% to 150% of baseline across a wide range of partial deflation. After full deflation, CFR transiently decreased to 45% to 95% of baseline. There was strong positive correlation (r > 0.85) between CFR and PMAP after full inflation, and positive correlation with partial inflation (r > 0.7). Carotid flow rate had strong correlation with the COMPASS with full REBOA (r > 0.85) and positive correlation with pREBOA (r > 0.65). CONCLUSION: Carotid flow rate is increased in a hemorrhagic model during full and partial inflation of the pREBOA and correlates well with PMAP. Carotid perfusion appears maintained across a wide range of pREBOA deflation and could be readily monitored with a handheld portable COMPASS device instead of a standard arterial line setup.

A REBOA Complication: EtCO2 Is Not Just a Marker of Cardiac Output.

We describe an as yet undescribed complication, namely, the perforation of the balloon at a distance from its introduction and the use of EtCO2 to suspect the diagnosis. Following a high-kinetic motorcycle accident, a 25-year-old patient was admitted in our level 1 trauma center, and benefited from a resuscitation thoracotomy followed by a REBOA catheter in zone 3. The use of a small caliber introducer could be responsible for balloon injury. EtCO2 is not only a marker of cardiac output and its sudden increase in this situation should raise questions about the recirculation of ischemia product and therefore the effectiveness of the occlusion balloon.

Novel intraperitoneal hemostasis device prolongs survival in a swine model of noncompressible abdominal hemorrhage.

BACKGROUND: Noncompressible torso hemorrhage (NCTH) of the abdomen is a challenge to rapidly control and treat in the prehospital and emergency department settings. In this pilot study, we developed a novel intraperitoneal hemostasis device (IPHD) prototype and evaluated its ability for slowing NCTH and prolonging survival in a porcine model of lethal abdominal multiorgan hemorrhage. METHODS: Yorkshire male swine (N = 8) were instrumented under general anesthesia for monitoring of hemodynamics and blood sampling. Animals were subjected to a 30% controlled arterial hemorrhage followed by lacerating combinations of the liver, spleen, and kidney. The abdomen was closed and after 2 minutes of NCTH, and the IPHD was inserted into the peritoneal cavity via an introducer (n = 5). The balloon was inflated and maintained for 60 minutes. At 60 minutes postdeployment, the balloon was deflated and removed, and blood resuscitation was initiated followed by gauze packing for hemostasis. The remaining animals (n = 3) were used as controls and subjected to the same injury without intervention. RESULTS: All animals managed with IPHD intervention (5 of 5 swine) survived the duration of the intervention period (60 minutes), while all control animals (3 of 3 swine) died at a time range of 15 to 43 minutes following organ injury (p = 0.0042). Animals receiving IPHD remained hemodynamically stable with a mean arterial pressure range of 44.86 to 55.10 mm Hg and experienced increased cardiac output and decreased shock index after treatment. Controls experienced hemodynamic decline in all parameters until endpoints were met. Upon IPHD deflation and removal, all treated animals began to hemorrhage again and expired within 2 to 132 minutes despite packing. CONCLUSION: Our data show that the IPHD concept is capable of prolonging survival by temporarily stanching lethal NCTH of the abdomen. This device may be an effective temporary countermeasure to NCTH of the abdomen that could be deployed in the prehospital environment or as a bridge to more advanced therapy.

A novel partial resuscitative endovascular balloon aortic occlusion device that can be deployed in zone 1 for more than 2 hours with minimal provider titration.

BACKGROUND: Hemorrhage is a leading cause of mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) can control hemorrhage, but distal ischemia, subsequent reperfusion injury, and the need for frequent balloon titration remain problems. Improved device design can allow for partial REBOA (pREBOA) that may provide hemorrhage control while also perfusing distally without need for significant provider titration. METHODS: Female Yorkshire swine (N = 10) were subjected to 40% hemorrhagic shock for 1 hour (mean arterial pressure [MAP], 28-32 mm Hg). Animals were then randomized to either complete aortic occlusion (ER-REBOA) or partial occlusion (novel pREBOA-PRO) without frequent provider titration or distal MAP targets. Detection of a trace distal waveform determined partial occlusion in the pREBOA-PRO arm. After 2 hours of zone 1 occlusion, the hemorrhaged whole blood was returned. After 50% autotransfusion, the balloon was deflated over a 10-minute period. Following transfusion, the animals were survived for 2 hours while receiving resuscitation based on objective targets: lactated Ringer's fluid boluses (goal central venous pressure, ≥ 6 mm Hg), a norepinephrine infusion (goal MAP, 55-60 mm Hg), and acid-base correction (goal pH, >7.2). Hemodynamic variables, arterial lactate, lactate dehydrogenase, aspartate aminotransferase, and creatinine levels were measured. RESULTS: All animals survived throughout the experiment, with similar increase in proximal MAPs in both groups. Animals that underwent partial occlusion had slightly higher distal MAPs. At the end of the experiment, the partial occlusion group had lower end levels of serum lactate (p = 0.006), lactate dehydrogenase (p = 0.0004) and aspartate aminotransferase (p = 0.004). Animals that underwent partial occlusion required less norepinephrine (p = 0.002), less bicarbonate administration (p = 0.006), and less fluid resuscitation (p = 0.042). CONCLUSION: Improved design for pREBOA can decrease the degree of distal ischemia and reperfusion injury compared with complete aortic occlusion, while providing a similar increase in proximal MAPs. This can allow pREBOA zone-1 deployment for longer periods without the need for significant balloon titration.

The Use of a Urinary Balloon Catheter to Control Hemorrhage From Penetrating Torso Trauma: A Single-Center Experience at a Major Inner-City Hospital Trauma Center.

INTRODUCTION: Use of a urinary catheter balloon tamponade (UCBT) in controlling traumatic hemorrhage is a frequently employed but infrequently described technique. We aim to discuss the experience of balloon tamponade as a bridge to definitive hemorrhage control in the operating room. METHODS: This is retrospective review at a single institution from January 2008 to December 2018. We identified patients with active bleeding from penetrating torso trauma in whom UCBT was used to tamponade bleeding. We used revised trauma score (RTS), injury severity score (ISS), and new trauma and injury severity score (TRISS) to quantify injury severity. All surviving patients required definitively hemorrhage control in the operating room. Primary endpoint was mortality at 24 hours and 30 days. RESULTS: Twenty-nine patients were managed with UCBT. Nine had hemorrhage controlled in the trauma bay, including 4 with neck trauma and 5 with cardiac trauma. Twenty patients had hemorrhage controlled in the operating room, including 15 with cardiac trauma and 5 with intra-abdominal hemorrhage. Mean RTS, ISS, and TRISS in this population were: 5.93, 19.31, and 83.78, respectively. Of the 9 patients treated in the trauma bay, 1 (11.1%) died in the first 24 hours and 2 died in the first 30 days (22.2%). Of the 20 patients treated in the operating room, 0 (0%) patients died in the first 24 hours and 3 died in the first 30 days (15.0%). CONCLUSION: UCBT is an effective tool that can be used to stabilize and bridge an actively bleeding patient to definitive hemorrhage control in the operating room.

First clinical multicenter experience with the new Scepter Mini microballoon catheter.

BACKGROUND: Balloon-assisted techniques can improve the endovascular treatment of cerebrospinal vascular malformations. The aim of this study was to report the first clinical multicenter experience with the new Scepter Mini dual-lumen microballoon catheter. METHODS: Patients with cerebral or spinal vascular malformations treated with the Scepter Mini at seven European neurovascular centers were retrospectively reviewed. Clinical data, angiographic features of the vascular malformations, procedural parameters including the type of application, navigability, technical failures, complications and embolization success were assessed. RESULTS: The usage of 34 Scepter Mini microballoon catheters in 20 patients was analyzed. Most treated malformations (80.0%) were cerebral arteriovenous malformations. Four different applications were reported: embolization via Scepter Mini (n=23, 67.6%), balloon-occlusion with simultaneous embolization via a second microcatheter (n=3, 8.8%), diagnostic angiography with simultaneous balloon-inflation for flow arrest (n=4, 11.8%), and navigation support (n=4, 11.8%). The mean diameter of the blood vessels in which the Scepter Mini was inflated was 1.9±0.5 mm. The navigability of the Scepter Mini was rated as 'easy' or 'very easy' in 88.2% of cases. Complete occlusion of the malformation was achieved in 60.9% of cases. Technical failures occurred in 4/23 embolization procedures, and all were related to insufficient stability of the balloon within the vessel. No complications related to the Scepter Mini were observed, while unrelated complications occurred in three patients (15.0%). CONCLUSIONS: The Scepter Mini is a promising new device for balloon-assisted embolization of cerebrospinal vascular malformations via small feeders. Beyond embolization, the Scepter Mini can also be used for other applications, such as superselective flow arrest and navigation support.

A contemporary assessment of devices for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): resource-specific options per level of care.

PURPOSE: Use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) as adjunct for temporary hemorrhage control in patients with exsanguinating torso hemorrhage is increasing. Characteristics of aortic occlusion balloons (AOB) are diverse and evolving as efforts are made to improve the technology. It is important to select a device that fits the requirements of the medical situation to minimize the risk of failure and complications. The aim of this study is to appraise guidance in the choice of an AOB in a specific situation. METHODS: We assessed 29 AOB for differences and outline possible advantages and disadvantages of each. Bending stiffness was measured with a three-point bending device. RESULTS: Diameter of the AOB ranged from 6 (ER-REBOA™) to 10 (Coda®-46) French. However, some need large-bore access sheaths up to 22 French (Fogarty®-45 and LeMaitre®-45) or even insertion via cut-down (Equalizer™-40). Bending stiffness varied from 0.08 N/mm (± 0.008 SD; Coda®-32) to 0.72 N/mm (± 0.024 SD; Russian prototype). Rescue Balloon™ showed kinking of the shaft at low bending pressures. The only non-compliant AOB is REBOA Balloon®. ER-REBOA™, Fogarty®, LeMaitre®, REBOA Balloon®, and Rescue Balloon™ are provided with external length marks to assist blind positioning. CONCLUSION: In resource-limited settings, a guidewire- and fluoroscopy-free, rather stiff device, such as ER-REBOA™, Fogarty®, and LeMaitre®, is warranted. Of these devices, ER-REBOA™ is the only catheter compatible with seven French sheaths and specifically designed for emergency hemorrhage control. Of the over-the-wire devices, Q50® has several features that facilitate use and reduce the risk of malplacement or vessel damage.

Mitigating Ischemia-Reperfusion Injury Using a Bilobed Partial REBOA Catheter: Controlled Lower-Body Hypotension.

BACKGROUND: Non-compressible torso hemorrhage (NCTH) is the leading cause of potentially preventable death on the battlefield. Resuscitative endovascular balloon occlusion of the aorta (REBOA) aims to restore central blood pressure and control NCTH below the balloon, but risks ischemia-reperfusion injury to distal organs when prolonged. We tested a bilobed partial REBOA catheter (pREBOA), which permits some of the blood to flow past the balloon. METHODS: Female swine (n = 37, 6 groups, n = 5-8/group), anesthetized and instrumented, were exponentially hemorrhaged 50% of estimated blood volume (all except time controls [TC]). Negative controls (NC) did not receive REBOA or resuscitation. Positive controls (PC) received retransfusion after 120 min. REBOA groups received REBOA for 120 min, then retransfusion. Balloon was fully inflated in the full REBOA group (FR), and was partially inflated in partial REBOA groups (P45 and P60) to achieve a distal systolic blood pressure of 45 mm Hg or 60 mm Hg. RESULTS: Aortic occlusion restored baseline values of proximal mean arterial pressure, cardiac output, and carotid flow in pREBOA groups. Lactate reached high values during occlusion in all REBOA groups (9.9 ±â€Š4.2, 8.0 ±â€Š4.1, and 10.7 ±â€Š2.9 for P45, P60, and FR), but normalized by 6 to 12 h post-deflation in the partial groups. All TC and P60 animals survived 24 h. The NC, PC, and P45 groups survived 18.2 ±â€Š9.5, 19.3 ±â€Š10.6, and 21.0 ±â€Š8.4 h. For FR animals mean survival was 6.2 ±â€Š5.8 h, significantly worse than all other animals (P < 0.01, logrank test). CONCLUSIONS: In this porcine model of hemorrhagic shock, animals undergoing partial REBOA for 120 min survived longer than those undergoing full occlusion.

Partial Resuscitative Endovascular Balloon Occlusion of the Aorta via the Tri-Lobe Balloon Catheter.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) provides a minimally invasive alternative to resuscitative thoracotomy. The high morbidity associated with prolonged aortic occlusion has given rise to the concept of partial REBOA (pREBOA). We evaluated the novel use of the GORE Tri-Lobe Balloon Catheter (GORE) as a functional pREBOA catheter and compared it with existing REBOA and pREBOA techniques in a porcine hemorrhagic shock model. MATERIALS AND METHODS: Fifteen male Yorkshire swine were subjected to hemorrhagic shock with zone 1 aortic occlusion via standard REBOA techniques or a partial occlusion approach using a prototype pREBOA or GORE catheter. Continuous invasive monitoring was performed and laboratory values were analyzed every 30 min. RESULTS: One animal from the GORE cohort was excluded because of early demise from nonstudy factors. Survival to 120 mins was comparable between all study groups: REBOA resulting in 40% survival, pREBOA 60%, and Gore 50% (P = 0.685). No differences in lactate, base deficit, and pH between the cohorts were demonstrated at all measured time points; however, trends toward more physiologic values were appreciated in the GORE and pREBOA cohorts. Urine output was significantly improved during the course of the study in the GORE cohort (8.77 mL/kg) versus REBOA (5.46 mL/kg) and pREBOA (4.48 mL/kg) (P = 0.001). CONCLUSIONS: The GORE Tri-Lobe Balloon Catheter represents a potentially viable and commercially available alternative device for pREBOA that may achieve survivable hemorrhage control while preventing lethal reperfusion injury. Further studies should be performed after instrument refinement with larger study populations to confirm this potential.