Joseph A. Posluszny

Multicenter review of diaphragm pacing in spinal cord injury: Successful not only in weaning from ventilators but also in bridging to independent respiration

BACKGROUND Ventilator-dependent spinal cord–injured (SCI) patients require significant resources related to ventilator dependence. Diaphragm pacing (DP) has been shown to successfully replace mechanical ventilators for chronic ventilator-dependent tetraplegics. Early use of DP following SCI has not been described. Here, we report our multicenter review experience with the use of DP in the initial hospitalization after SCI. METHODS Under institutional review board approval for humanitarian use device, we retrospectively reviewed our multicenter nonrandomized interventional protocol of laparoscopic diaphragm motor point mapping with electrode implantation and subsequent diaphragm conditioning and ventilator weaning. RESULTS Twenty-nine patients with an average age of 31 years (range, 17–65 years) with only two females were identified. Mechanism of injury included motor vehicle collision (7), diving (6), gunshot wounds (4), falls (4), athletic injuries (3), bicycle collision (2), heavy object falling on spine (2), and motorcycle collision (1). Elapsed time from injury to surgery was 40 days (range, 3–112 days). Seven (24%) of the 29 patients who were evaluated for the DP placement had nonstimulatable diaphragms from either phrenic nerve damage or infarction of the involved phrenic motor neurons and were not implanted. Of the stimulatable patients undergoing DP, 72% (16 of 22) were completely free of ventilator support in an average of 10.2 days. For the remaining six DP patients, two had delayed weans of 180 days, three had partial weans using DP at times during the day, and one patient successfully implanted went to a long-term acute care hospital and subsequently had life-prolonging measures withdrawn. Eight patients (36%) had complete recovery of respiration, and DP wires were removed. CONCLUSION Early laparoscopic diaphragm mapping and DP implantation can successfully wean traumatic cervical SCI patients from ventilator support. Early laparoscopic mapping is also diagnostic in that a nonstimulatable diaphragm is a convincing evidence of an inability to wean from ventilator support, and long-term ventilator management can be immediately instituted. LEVEL OF EVIDENCE Therapeutic study, level V.

Surgical burn wound infections and their clinical implications

Typically, burn wound infections are classified by the organisms present in the wound within the first several days after injury or later by routine surveillance cultures. With universal acceptance of early excision and grafting, classification of burn wound colonization in unexcised burn wounds is less relevant, shifting clinical significance to open burn-related surgical wound infections (SWIs). To better characterize SWIs and their clinical relevance, the authors identified the pathogens responsible for SWIs, their impact on rates of regrafting, and the relationship between SWI and nosocomial infection (NI) pathogens. Epidemiologic and clinical data for 71 adult patients with ≥20% TBSA burn were collected. After excision and grafting, if a grafted site had clinical characteristics of infection, a wound culture swab was obtained and the organism identified. Surveillance cultures were not obtained. SWI pathogen, anatomic location, postburn day of occurrence, and need for regrafting were compiled. A positive culture obtained from an isolated anatomic location at any time point after excision and grafting of that location was considered a distinct infection. Pathogens responsible for NIs (urinary tract infections, pneumonia, bloodstream and catheter-related bloodstream infections, pseudomembranous colitis, and donor site infections) and their postburn day were identified. The profiles of SWI pathogens and NI pathogens were then compared. Of the 71 patients included, 2 withdrew, 6 had no excision or grafting performed, and 1 had incomplete data. Of the remaining 62 patients, 24 (39%) developed an SWI. In these 24 patients, 70 distinct infections were identified, of which 46% required regrafting. Candida species (24%), Pseudomonas aeruginosa (22%), Serratia marcescens (11%), and Staphylococcus aureus (11%) comprised the majority of pathogens. Development of an SWI with the need for regrafting increased overall length of stay, area of autograft, number of operative events, and was closely associated with the number of NIs. The %TBSA burn and depth of the burn were the main risk factors for SWI with need for regrafting. The SWI pathogen was identified as an NI pathogen 56% of the time, with no temporal correlation between shared SWI and NI pathogens. SWIs are commonly found in severely burned patients and are associated with regrafting. As a result, patients with SWIs are subjected to increased operative events, autograft placement, and increased length of hospitalization. In addition, the presence of an SWI may be a risk factor for development of NIs.

Anemia of Thermal Injury: Combined Acute Blood Loss Anemia and Anemia of Critical Illness

Anemia is a pervasive and difficult-to-treat consequence of a severe burn injury. The most effective method of correcting anemia is the transfusion of packed red blood cells, but this therapy is not without complications. Surgical techniques including tourniquets and epinephrine tumescence have reduced blood loss and stricter thresholds have limited transfusions, but for severe burns, transfusion requirements are still massive. In this review of the current literature of anemia of thermal injury, we will provide a new framework for addressing this anemia and will show how this approach may help to develop better interventions and further reduce transfusion rates.

Outcome of Adult Respiratory Failure Patients Receiving Prolonged (≥14 Days) ECMO.

Objective:To examine the outcomes of prolonged (≥14 days) extracorporeal membrane oxygenation (P-ECMO) for adult severe respiratory failure and to assess characteristics associated with survival. Background:The use of ECMO for treatment of severe respiratory adult patients is associated with overall survival rates of 50% to 70% with median ECMO duration of 10 days. No prior multi-institutional studies have examined outcomes of P-ECMO for severe respiratory failure. Methods:Data on all adult (≥18 years) patients who required P-ECMO for severe respiratory failure from 1989 to 2013 were extracted from the Extracorporeal Life Support Organization international multi-institutional registry. We examined outcomes over 23 years and compared the 2 more recent time periods of 1989 to 2006 versus 2007 to 2013. Results:Up to 974 patients, mean age 40.2 (18–83) years, had ECMO duration of mean 25.2 days/median 21.0 days (range: 14–208 days). Venovenous ECMO support was most common (venovenous: 79.5%, venoarterial: 9.9%). Reason for ECMO discontinuation included native lung recovery (54%), organ failure (23.7%), family request (6.7%), hemorrhage (2.7%), and diagnosis incompatible with life (5.6%). Forty patients (4.1%) underwent lung transplant with 50% postoperative in-hospital mortality. Increased prevalence of P-ECMO was noted with 72% (701/974) of all cases reported since 2008. Survival to hospital discharge was 45.4% (443/974) and did not vary with ECMO duration. Multivariate logistic regression analysis confirmed that P-ECMO patients 2007 to 2013 had a lower risk of death [odds ratio (OR): 0.650; 95% confidence interval (CI), 0.454–0.929; P = 0.010] compared with 1989 to 2006. Factors independently associated with survival were younger age (OR: 0.983; 95% CI, 0.974–0.993; P < 0.001) and lower PaCO2 (OR, 0.991; 95% CI, 0.986–0.996; P < 0.001). Conclusions:Prolonged ECMO use for adult respiratory failure was associated with a lower (45.4%) hospital survival rate, compared with prior reported survival rates of short duration ECMO. Prolonged ECMO survival significantly increased in recent years, and increasing ECMO duration did not alter the survival fraction in the 1989 to 2013 study cohort. Although P-ECMO survival rates are less than short ECMO runs, P-ECMO support is justified.

High MafB expression following burn augments monocyte commitment and inhibits DC differentiation in hemopoietic progenitors

We have previously shown that perturbed bone marrow progenitor development promotes hyporesponsive monocytes following experimental burn sepsis. Clinical and experimental sepsis is associated with monocyte deactivation and depletion of mDCs. Decrease in circulating DCs is reported in burn patients who develop sepsis. In our 15% TBSA scald burn model, we demonstrate a significant reduction in the circulating MHC‐II+ population and mDCs (Gr1negCD11b+CD11c+) with a corresponding decrease in bone marrow MHC‐II+ cells and mDCs for up to 14 days following burn. We explored the underlying mechanism(s) that regulate bone marrow development of monocytes and DCs following burn injury. We found a robust bone marrow response with a significant increase in multipotential HSCs (LSK) and bipotential GMPs following burn injury. GMPs from burn mice exhibit a significant reduction in GATA‐1, which is essential for DC development, but express high levels of MafB and M‐CSFRs, both associated with monocyte production. GMPs obtained from burn mice differentiated 1.7 times more into Mφ and 1.6‐fold less into DCs compared with sham. Monocytes and DCs expressed 50% less MHC‐II in burn versus sham. Increased monocyte commitment in burn GMPs was a result of high MafB and M‐CSFR expressions. Transient silencing of MafB (siRNA) in GMP‐derived monocytes from burn mice partially restored DC differentiation deficits and increased GATA‐1 expression. We provide evidence that high MafB following burn plays an inhibitory role in monocyte‐derived DC differentiation by regulating M‐CSFR and GATA‐1 expressions.

Classifying Transfusions Related to the Anemia of Critical Illness in Burn Patients

BACKGROUND Critically ill patients require transfusions because of acute blood loss and the anemia of critical illness. In critically ill burn patients, typically, no distinction is made between transfusions related to acute surgical blood loss and those related to the anemia of critical illness. We sought to identify the percentage of blood transfusions due to the anemia of critical illness and the clinical characteristics associated with these transfusions in severely burned patients. METHODS Sixty adult patients with ≥20% total body surface area (TBSA) burn who were transfused at least 1 unit of packed red blood cells during their hospitalization were studied. Clinical variables including age, %TBSA burn, Acute Physiology and Chronic Health Evaluation (APACHE) II score, number of ventilator days, inhalation injury, and number of operative events were correlated with the total number of packed red blood cell units and percentage of nonsurgical transfusions in these patients. Nonsurgical transfusions were defined as transfusions occurring after postoperative day 1 for each distinct operative event and were classified as being caused by the anemia of critical illness. RESULTS Patients were transfused an average of 16.6 units ± 21.2 units. Nonsurgical transfusions accounted for 52% of these transfusions. APACHE II score, %TBSA burn, number of ventilator days, and number of operative events, all correlated with total transfusions. However, nonsurgical transfusions correlated with only APACHE II score (p = 0.01) and number of ventilator days (p = 0.03). There was no correlation between nonsurgical transfusions and other clinical variables. CONCLUSION The anemia of critical illness is responsible for >50% of all transfusions in severely burned patients. The initial severity of critical illness (APACHE II score) and duration of the critical illness (number of ventilator days) correlated with transfusions related to anemia of critical illness. Further investigation into the specific risk factors for these transfusions may help to develop strategies to further reduce transfusion rates.

Burn injury dampens erythroid cell production through reprioritizing bone marrow hematopoietic response.

BACKGROUND Anemia in burn patients is due to surgical blood loss and anemia of critical illness. Because the commitment paradigm of common bone marrow progenitors dictates the production of erythroid, myeloid, and lymphoid cells, we hypothesized that skewed bone marrow lineage commitment decreases red cell production and causes anemia after a burn injury. METHODS After anesthesia, B(6)D(2)F(1) mice received a 15% total body surface area dorsal scald burn. The sham group did not receive scald burn. Femoral bone marrow was harvested on 2, 5, 7, 14, and 21 postburn days (PBD). Total bone marrow cells were labeled with specific antibodies to erythroid (CD71/Ter119), myeloid (CD11b), and lymphoid (CD19) lineages and analyzed by flow cytometry. To test whether erythropoietin (EPO) could increase red blood cell production, EPO was administered to sham and burn animals and their reticulocyte response was measured on PBD 2 and PBD 7. RESULTS Burn injury reduced the erythroid cells of the bone marrow from 35% in sham to 17% by PBD 5 and remained at similar level until PBD 21. Myeloid cells, however, increased from 42% in sham to 60% on PBD 5 and 77% on PBD 21. Burn injury reduced reticulocyte counts on PBD 2 and PBD 7 indicating that the erythroid compartment is severely depleted. This depleted compartment, however, responded to EPO but was not sufficient to change red cell production. CONCLUSION Burn injury skews the bone marrow hematopoietic commitment away from erythroid and toward myeloid cells. Shrinkage of the erythroid compartment contributes to resistance to EPO and the anemia of critical illness.

How do we treat life‐threatening anemia in a Jehovah's Witness patient?

The refusal of allogeneic human blood and blood products by Jehovahs Witness (JW) patients complicates the treatment of life‐threatening anemia. For JW patients, when hemoglobin (Hb) levels decrease beyond traditional transfusion thresholds (<7 g/dL), alternative methods to allogeneic blood transfusion can be utilized to augment erythropoiesis and restore endogenous Hb levels. The use of erythropoietin‐stimulating agents and intravenous iron has been shown to restore red blood cell and Hb levels in JW patients, although these effects may be significantly delayed. When JW patients have evidence of life‐threatening anemia (Hb <5 g/dL), oxygen‐carrying capacity can be supplemented with the administration of Hb‐based oxygen carriers (HBOCs). Although HBOCs are not Food and Drug Administration (FDA) approved, they may be obtained and administered with FDA, institutional review board, and patient approval. We describe a protocol‐based algorithm to the management of life‐threatening anemia in JW patients and review time to anemia reversal and patient outcomes using this approach.

Perturbed MafB/GATA1 axis after burn trauma bares the potential mechanism for immune suppression and anemia of critical illness.

Patients who survive initial burn injury are susceptible to nosocomial infections. Anemia of critical illness is a compounding factor in burn patients that necessitates repeated transfusions, which further increase their susceptibility to infections and sepsis. Robust host response is dependent on an adequate number and function of monocytes/macrophages and dendritic cells. In addition to impaired RBC production, burn patients are prone to depletion of dendritic cells and an increase in deactivated monocytes. In steady‐state hematopoiesis, RBCs, macrophages, and dendritic cells are all generated from a common myeloid progenitor within the bone marrow. We hypothesized in a mouse model of burn injury that an increase in myeloid‐specific transcription factor V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B at the common myeloid progenitor stage steers their lineage potential away from the megakaryocyte erythrocyte progenitor production and drives the terminal fate of common myeloid progenitors to form macrophages vs. dendritic cells, with the consequences being anemia, monocytosis, and dendritic cell deficits. Results indicate that, even though burn injury stimulated bone marrow hematopoiesis by increasing multipotential stem cell production (LinnegSca1poscKitpos), the bone marrow commitment is shifted away from the megakaryocyte erythrocyte progenitor and toward granulocyte monocyte progenitors with corresponding alterations in peripheral blood components, such as hemoglobin, hematocrit, RBCs, monocytes, and granulocytes. Furthermore, burn‐induced V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B in common myeloid progenitors acts as a transcriptional activator of M‐CSFR and a repressor of transferrin receptors, promoting macrophages and inhibiting erythroid differentiations while dictating a plasmacytoid dendritic cell phenotype. Results from small interfering RNA and gain‐of‐function (gfp‐globin transcription factor 1 retrovirus) studies indicate that targeted interventions to restore V‐maf musculoaponeurotic fibrosarcoma oncogene homolog B/globin transcription factor 1 balance can mitigate both immune imbalance and anemia of critical illness.

Trauma to the Pelvis: Injuries to the Rectum and Genitourinary Organs

Pelvic trauma is associated with high mortality rates. Blunt pelvic injuries from high-energy mechanisms are often associated with pelvic fractures and injuries to the rectum and genitourinary (GU) tract. In addition, due to close anatomic proximity, penetrating pelvic trauma can injure the bony pelvis, rectum, and GU tract concomitantly. As a result, the assessment and management of pelvic trauma requires a multifaceted approach involving orthopedics, trauma surgery and urology.