Daniel N. Holena

A Review of the Fundamental Principles and Evidence Base in the Use of Extracorporeal Membrane Oxygenation (ECMO) in Critically Ill Adult Patients

Extracorporeal membrane oxygenation (ECMO) comprises a commonly used method of extracorporeal life support. It has proven efficacy and is an accepted modality of care for isolated respiratory or cardiopulmonary failure in neonatal and pediatric populations. In adults, there are conflicting studies regarding its benefit, but it is possible that ECMO may be beneficial in certain adult populations beyond postcardiotomy heart failure. As such, all intensivists should be familiar with the evidence-base and principles of ECMO in adult population. The purpose of this article is to review the evidence and to describe the fundamental steps in initiating, adjusting, troubleshooting, and terminating ECMO so as to familiarize the intensivist with this modality.

Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness.

BACKGROUND Critical illness is characterized by hypoferremia, iron-deficient erythropoiesis (IDE), and anemia. The relative risks and benefits of iron supplementation in this setting are unknown. METHODS Anemic, critically ill surgical patients with an expected intensive care unit length of stay (ULOS) >or= 5 days were randomized to either enteral iron supplementation (ferrous sulfate 325 mg three times daily) or placebo until hospital discharge. Outcomes included hematocrit, iron markers (i.e., serum concentrations of iron, ferritin, and erythrocyte zinc protoporphyrin [eZPP]), red blood cell (RBC) transfusion, transfusion rate (mL RBC/study day), nosocomial infection, antibiotic days, study length of stay (LOS), ULOS, and death. Iron-deficient erythropoiesis was defined as an elevated eZPP concentration. RESULTS Two hundred patients were randomized; 97 received iron, and 103 received placebo. Socio-demographics, baseline acuity, hematocrit, and iron markers were similar in the two groups. No differences were observed between the iron and placebo groups with respect to either hematocrit or iron markers following up to 28 days. However, patients treated with iron were significantly less likely to receive an RBC transfusion (29.9% vs. 44.7%, respectively; p = 0.03) and had a significantly lower transfusion rate (22.0 mL/day vs. 29.9 mL/day; p = 0.03). Subgroup analysis revealed that these differences were observed in patients with baseline IDE only. Iron and placebo groups did not differ with respect to incidence of infection (46.8% vs. 48.9%; p = 0.98), antibiotic days (14 vs. 16; p = 0.45), LOS (14 vs. 16 days; p = 0.24), ULOS (12 vs. 14 days; p = 0.69), or mortality rate (9.4% vs. 9.9%; p = 0.62). CONCLUSIONS Enteral iron supplementation of anemic, critically ill surgical patients does not increase the risk of infection and may benefit those with baseline IDE by decreasing the risk of RBC transfusion. A trial comparing enteral and parenteral iron supplementation in this setting is warranted (ClinicalTrials.gov number, NCT00450177).

African American race, obesity, and blood product transfusion are risk factors for acute kidney injury in critically ill trauma patients☆

PURPOSE Acute kidney injury (AKI) is a common source of morbidity after trauma. We sought to determine novel risk factors for AKI, by Acute Kidney Injury Network (AKIN) criteria, in critically ill trauma patients. MATERIALS AND METHODS A prospective cohort of 400 patients admitted to the intensive care unit of a level 1 trauma center was followed for the development of AKI over 5 days. RESULTS Acute kidney injury developed in 147 (36.8%) of 400 patients. In multivariable regression analysis, independent risk factors for AKI included African American race (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.08-3.18; P = .024), body mass index of 30 kg/m(2) or greater (OR, 4.72 versus normal body mass index; 95% CI, 2.59-8.61; P < .001), diabetes mellitus (OR, 3.26; 95% CI, 1.30-8.20; P = .012), abdominal Abbreviated Injury Scale score of 4 or more (OR, 3.78; 95% CI, 1.79-7.96; P < .001), and unmatched packed red blood cells administered during resuscitation (OR, 1.13 per unit; 95% CI, 1.04-1.23; P = .004). Acute Kidney Injury Network stages 1, 2, and 3 were associated with hospital mortality rates of 9.8%, 13.7%, and 30.4%, respectively, compared with 3.8% for those without AKI (P < .001). CONCLUSIONS Acute kidney injury in critically ill trauma patients is associated with substantial mortality. The findings of African American race, obesity, and blood product administration as independent risk factors for AKI deserve further study to elucidate underlying mechanisms.

A multicenter, randomized clinical trial of IV iron supplementation for anemia of traumatic critical illness

Objective:To evaluate the efficacy of IV iron supplementation of anemic, critically ill trauma patients. Design:Multicenter, randomized, single-blind, placebo-controlled trial. Setting:Four trauma ICUs. Patients:Anemic (hemoglobin < 12 g/dL) trauma patients enrolled within 72 hours of ICU admission and with an expected ICU length of stay of more than or equal to 5 days. Interventions:Randomization to iron sucrose 100 mg IV or placebo thrice weekly for up to 2 weeks. Measurements and Main Results:A total of 150 patients were enrolled. Baseline iron markers were consistent with functional iron deficiency: 134 patients (89.3%) were hypoferremic, 51 (34.0%) were hyperferritinemic, and 64 (42.7%) demonstrated iron-deficient erythropoiesis as evidenced by an elevated erythrocyte zinc protoporphyrin concentration. The median baseline transferrin saturation was 8% (range, 2–58%). In the subgroup of patients who received all six doses of study drug (n = 57), the serum ferritin concentration increased significantly for the iron as compared with placebo group on both day 7 (808.0 ng/mL vs 457.0 ng/mL, respectively, p < 0.01) and day 14 (1,046.0 ng/mL vs 551.5 ng/mL, respectively, p < 0.01). There was no significant difference between groups in transferrin saturation, erythrocyte zinc protoporphyrin concentration, hemoglobin concentration, or packed RBC transfusion requirement. There was no significant difference between groups in the risk of infection, length of stay, or mortality. Conclusions:Iron supplementation increased the serum ferritin concentration significantly, but it had no discernible effect on transferrin saturation, iron-deficient erythropoiesis, hemoglobin concentration, or packed RBC transfusion requirement. Based on these data, routine IV iron supplementation of anemic, critically ill trauma patients cannot be recommended (NCT 01180894).

Racial disparity in analgesic treatment for ED patients with abdominal or back pain.

OBJECTIVE Research on how race affects access to analgesia in the emergency department (ED) has yielded conflicting results. We assessed whether patient race affects analgesia administration for patients presenting with back or abdominal pain. METHODS This is a retrospective cohort study of adults who presented to 2 urban EDs with back or abdominal pain for a 4-year period. To assess differences in analgesia administration and time to analgesia between races, Fisher exact and Wilcoxon rank sum test were used, respectively. Relative risk regression was used to adjust for potential confounders. RESULTS Of 20,125 patients included (mean age, 42 years; 64% female; 75% black; mean pain score, 7.5), 6218 (31%) had back pain and 13,907 (69%) abdominal pain. Overall, 12,109 patients (60%) received any analgesia and 8475 (42%) received opiates. Comparing nonwhite (77 %) to white patients (23%), nonwhites were more likely to report severe pain (pain score, 9-10) (42% vs 36%; P < .0001) yet less likely to receive any analgesia (59% vs 66%; P < .0001) and less likely to receive an opiate (39% vs 51%; P < .0001). After controlling for age, sex, presenting complaint, triage class, admission, and severe pain, white patients were still 10% more likely to receive opiates (relative risk, 1.10; 95% confidence interval, 1.06-1.13). Of patients who received analgesia, nonwhites waited longer for opiate analgesia (median time, 98 vs 90 minutes; P = .004). CONCLUSIONS After controlling for potential confounders, nonwhite patients who presented to the ED for abdominal or back pain were less likely than whites to receive analgesia and waited longer for their opiate medication.

Classifying errors in preventable and potentially preventable trauma deaths: a 9-year review using the Joint Commission's standardized methodology

BACKGROUND Benchmarking and classification of avoidable errors in trauma care are difficult as most reports classify errors using variable locally derived schemes. We sought to classify errors in a large trauma population using standardized Joint Commission taxonomy. METHODS All preventable/potentially preventable deaths identified at an urban, level-1 trauma center (January 2002 to December 2010) were abstracted from the trauma registry. Errors deemed avoidable were classified within the 5-node (impact, type, domain, cause, and prevention) Joint Commission taxonomy. RESULTS Of the 377 deaths in 11,100 trauma contacts, 106 (7.7%) were preventable/potentially preventable deaths related to 142 avoidable errors. Most common error types were in clinical performance (inaccurate diagnosis). Error domain involved primarily the emergency department (therapeutic interventions), caused mostly by knowledge deficits. Communication improvement was the most common mitigation strategy. CONCLUSION Standardized classification of errors in preventable trauma deaths most often involve clinical performance in the early phases of care and can be mitigated with universal strategies.

Heterogeneous phenotypes of acute respiratory distress syndrome after major trauma.

RATIONALE Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that can develop at various times after major trauma. OBJECTIVES To identify and characterize distinct phenotypes of ARDS after trauma, based on timing of syndrome onset. METHODS Latent class analyses were used to identify patterns of ARDS onset in a cohort of critically ill trauma patients. Identified patterns were tested for associations with known ARDS risk factors and associations were externally validated at a separate institution. Eleven plasma biomarkers representing pathophysiologic domains were compared between identified patterns in the validation cohort. MEASUREMENTS AND MAIN RESULTS Three patterns of ARDS were identified; class I (52%) early onset on Day 1 or 2, class II (40%) onset on Days 3 and 4, and class III (8%) later onset on Days 4 and 5. Early-onset ARDS was associated with higher Abbreviated Injury Scale scores for the thorax (P < 0.001), lower lowest systolic blood pressure before intensive care unit admission (P = 0.003), and a greater red blood cell transfusion requirement during resuscitation (P = 0.030). In the external validation cohort, early-onset ARDS was also associated with a higher Abbreviated Injury Scale score for the thorax (P = 0.001) and a lower lowest systolic blood pressure before intensive care unit enrollment (P = 0.006). In addition, the early-onset phenotype demonstrated higher plasma levels of soluble receptor for advanced glycation end-products and angiopoietin-2. CONCLUSIONS Degree of hemorrhagic shock and severity of thoracic trauma are associated with an early-onset phenotype of ARDS after major trauma. Lung injury biomarkers suggest a dominant alveolar-capillary barrier injury pattern in this phenotype.

Transfer status: A risk factor for mortality in patients with necrotizing fasciitis

BACKGROUND Necrotizing fasciitis (NF) is a rapidly progressive disease that requires urgent surgical debridement for survival. Interhospital transfer (IT) may be associated with delay to operation, which could increase mortality. We hypothesized that mortality would be higher in patients undergoing surgical debridement for necrotizing fasciitis after IT compared to Emergency Department (ED) admission. METHODS We performed a retrospective cohort analysis from 2000-2006 using the Nationwide Inpatient Sample. Inclusion criteria were age >18 years, primary diagnosis of NF, and surgical therapy within 72 hours of admission. Logistic regression was used to assess the relationship between admission source, patient and hospital variables, and mortality. RESULTS We identified 9,958 cases over the study period. Patients in the ED group were more likely to be nonwhite and of lower income when compared with patients in the IT group. Unadjusted mortality was higher in the IT group than ED group (15.5% vs 8.7%, P < .001). After adjusting for potential confounders, odds of mortality were still greater in the IT (OR 2.04, CI 95% 1.60-2.59, P < .001). CONCLUSION Interhospital transfer is associated with increased risk of in-hospital mortality after surgical therapy for NF, a finding which persists after controlling for patient and hospital level variables.

Screening for thoracolumbar spinal injuries in blunt trauma: An Eastern Association for the Surgery of Trauma practice management guideline

BACKGROUND Thoracolumbar spine (TLS) injuries have an incidence rate of 5% in blunt trauma patients. The Eastern Association for the Surgery of Trauma published Practice Management Guidelines for the Screening of Thoracolumbar Spine Fracture in 2007. The Practice Management Guidelines Committee was assembled to reevaluate the literature. METHODS A search of the United States National Library of Medicine and the National Institutes of Health database was performed using MEDLINE through PubMed (www.pubmed.gov). The search retrieved English-language articles from March 2005 to December 2011 that referenced traumatic TLS injuries and fractures. The questions posed were the following: (1) What is the appropriate imaging modality to screen patients for TLS injuries? (2) Which trauma patients require radiographic screening for TLS injuries? (3)Does a patient who is awake and alert without distracting injuries require radiologic workup to rule out TLS injuries? RESULTS Thirty-seven articles that referenced traumatic TLS injuries in association with screening published between March 2005 and December 2011 were collected and disseminated to the committee. Twelve were found to be relevant. Nine publications from the previous 2006 guidelines were reviewed and referenced to create and validate the updated guidelines. CONCLUSION Practice patterns have changed regarding screening blunt trauma patients for TLS injuries. Software reformatted multidetector computed tomographic scans are more sensitive and accurate than plain films. Multidetector computed tomographic scans have become the screening modality of choice and the criterion standard in screening for TLS injuries. The literature supports a Level 1 recommendation to validate this based on a preponderance of Class II data. Patients without altered mentation or significant mechanism may be excluded by clinical examination without imaging. Patients with gross neurologic deficits or concerning clinical examination findings with negative imaging should receive a magnetic resonance imaging expediently, and the spine service should be consulted.

Hyperbaric oxygen therapy in necrotizing soft tissue infections

BACKGROUND Surgical debridement and antibiotics are the mainstays of therapy for patients with necrotizing soft tissue infections (NSTIs), but hyperbaric oxygen therapy (HBO) is often used as an adjunctive measure. Despite this, the efficacy of HBO remains unclear. We hypothesized that HBO would have no effect on mortality or amputation rates. METHODS We performed a retrospective analysis of our institutional experience from 2005 to 2009. Inclusion criteria were age > 18 y and discharge diagnosis of NSTI. We abstracted baseline demographics, physiology, laboratory values, and operative course from the medical record. The primary endpoint was in-hospital mortality; the secondary endpoint was extremity amputation rate. We compared baseline variables using Mann-Whitney, chi-square, and Fishers exact test, as appropriate. Significance was set at P < 0.05. RESULTS We identified 80 cases over the study period. The cohort was 54% male (n = 43) and 53% white (n = 43), and had a mean age of 55 ± 16 y. There were no significant differences in demographics, physiology, or comorbidities between groups. In-hospital mortality was not different between groups (16% in the HBO group versus 19% in the non-HBO group; P = 0.77). In patients with extremity NSTI, the amputation rate did not differ significantly between patients who did not receive HBO and those who did (17% versus 25%; P = 0.46). CONCLUSIONS Hyperbaric oxygen therapy does not appear to decrease in-hospital mortality or amputation rate after in patients with NSTI. There may be a role for HBO in treatment of NSTI; nevertheless, consideration of HBO should never delay operative therapy. Further evidence of efficacy is necessary before HBO can be considered the standard of care in NSTI.