Critical Surgical Illness Research Articles

Thyroid hormone changes in critical surgical illness: a narrative review

The systemic response to stress caused by a critical surgical illness is characterized by a series of events that precede metabolic and neuroendocrine dysregulation. However, the relevance of theclassically described 'stress response' is now highly questionable in an era where profound physiological deconditioning is common in critically ill, surgical and non-surgical patients. Common assessment techniques do not accurately reflect the integrity of the hypothalamic-pituitary-thyroid axis in the course of a critical chronic disease state. The clinical presentation ismostly masked by symptoms of the underlying critical illness when plasma thyroid hormone concentrations are altered. The frequent development of multimorbidity in critically ill patients is the reason for the need for a more detailed analysis of the neuroendocrine model of activation. Basic scientific studies suggest that low levels of circulating thyroid hormones in the acute phase are an adaptive process, but the chronic condition could directly cause organ damage. Here, we review factors that have emerged to challenge the conventional model of euthyroid sick syndrome (ESS) in the surgically critically ill as an adaptive process, and suggest that the stage of the critical illness is an important consideration in the critically ill. Examining the stressresponse in the critically ill presents opportunities to improve outcomes through improved understanding of the neuroendocrine aspects.

Shock Severity Classification and Mortality in Adults With Cardiac, Medical, Surgical, and Neurological Critical Illness

ObjectiveTo evaluate whether the Society for Cardiovascular Angiography and Interventions (SCAI) Shock Classification could perform risk stratification in a mixed cohort of intensive care unit (ICU) patients, similar to its validation in patients with acute cardiac disease. MethodsWe included 21,461 adult Mayo Clinic ICU patient admissions from December 1, 2014, to February 28, 2018, including cardiac ICU (16.7%), medical ICU (37.4%), neurosciences ICU (27.7%), and surgical ICU (18.2%). The SCAI Shock Classification (a 5-stage classification from no shock [A] to refractory shock [E]) was assigned in each 4-hour period during the first 24 hours of ICU admission. ResultsThe median age was 65 years, and 43.2% were female. In-hospital mortality occurred in 1611 (7.5%) patients, with a stepwise increase in in-hospital mortality in each higher maximum SCAI Shock stage overall: A, 4.0%; B, 4.6%; C, 7.0%; D, 13.9%; and E, 40.2%. The SCAI Shock Classification provided incremental mortality risk stratification in each ICU, with the best performance in the cardiac ICU and the worse performance in the neurosciences ICU. The SCAI Shock Classification was associated with higher adjusted in-hospital mortality (adjusted odds ratio, 1.32 per each stage; 95% CI, 1.24 to 1.41; P<.001); this association was not observed in the neurosciences ICU when considered separately. ConclusionThe SCAI Shock Classification provided incremental mortality risk stratification beyond established prognostic markers across the spectrum of medical and surgical critical illness, proving utility outside its original intent.

Does administration of vaginal estrogens increase the risk of venous thromboembolism: A case-control study.

Does administration of vaginal estrogens increase the risk of venous thromboembolism: A case-control study.

Palliative care for pediatric intensive care patients and families.

Children with medical or surgical critical illness or injury require skillful attention to physical, emotional, psychological, and spiritual needs, whereas their families need support and guidance in facing life-threatening or life-changing events and gut-wrenching decisions. This article reviews current evidence and best practices for integrating palliative care into the pediatric intensive care unit (PICU), with a focus on surgical patients. Palliative care is best integrated in a tiered approach, with primary palliative care provided by the PICU and surgical providers for all patients and families, including basic symptom management, high-quality communication, and end-of-life care. Secondary and tertiary levels of care involve unit or team-based 'champions' with additional expertise, and subspecialty palliative care teams, respectively. PICU and surgical providers should be able to provide primary palliative care, to identify patients and families for whom a palliative care consult would be helpful, and should be comfortable introducing the concept of palliative care to families. This review provides a framework and tools to enable PICU and surgical providers to integrate palliative care best practices into patient and family care.

Systematic review of oxygenation and clinical outcomes to inform oxygen targets in critically ill trauma patients.

Oxygen therapy is frequently administered to critically ill trauma patients to avoid hypoxia, but optimal oxygenation strategies are not clear. We conducted a systematic review of oxygen targets and clinical outcomes in trauma and critically ill patients. We searched Ovid MEDLINE, Cochrane Library, Embase, and Web of Science Core Collection from 1946 through 2017. Our initial search yielded 14,774 articles with 209 remaining after abstract review. We reviewed full text articles of human subjects with conditions of interest, an oxygen exposure or measurement, and clinical outcomes, narrowing the review to 43 articles. We assessed article quality using Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. Of the 43 final studies meeting inclusions criteria, 17 focused on trauma and 26 studies focused on medical and/or surgical critical illness without trauma specifically. Four trauma studies supported lower oxygenation/normoxia, two supported higher oxygenation, and 11 supported neither normoxia nor higher oxygenation (five neutral and six supported avoidance of hypoxia). Fifteen critical illness studies supported lower oxygenation/normoxia, one supported higher oxygenation, and 10 supported neither normoxia nor higher oxygenation (nine neutral and one supported avoidance of hypoxia). We identified seven randomized controlled trials (four high quality, three moderate quality). Of the high-quality randomized controlled trials (none trauma-related), one supported lower oxygenation/normoxia and three were neutral. Of the moderate-quality randomized controlled trials (one trauma-related), one supported higher oxygenation, one was neutral, and one supported avoidance of hypoxia. We identified few trauma-specific studies beyond traumatic brain injury; none were high quality. Extrapolating primarily from nontrauma critical illness, reduced oxygen administration targeting normoxia in critically ill trauma patients may result in better or equivalent clinical outcomes. Additional trauma-specific trials are needed to determine the optimal oxygen strategy in critically injured patients. Systematic review, level IV.

Urinary Mitochondrial DNA Levels Identify Acute Kidney Injury in Surgical Critical Illness Patients.

Recent studies showed that mitochondrial injury and mitochondrial DNA (mtDNA) damage are associated with the initiation and progression of acute kidney injury (AKI). However, practical limitations of existing assays of mitochondrial function have limited our ability to study the link between mitochondrial dysfunction and renal injury. Therefore, we evaluated urinary mtDNA (UmtDNA) as a biomarker of AKI in critical illness patients. DNA was isolated from urine samples in surgical intensive care unit (SICU) patients and quantified by quantitative polymerase chain reaction (PCR). Correlation analyses showed the relationships between the UmtDNA and several biomarkers of renal dysfunction. Moreover, we evaluated the predictive and diagnostic values of UmtDNA in newly developed AKI, renal replacement therapy (RRT), and hospital mortality using receiver operating characteristics curves. MtDNA were expressed as PCR threshold cycle (Tc) number. Lower Tc indicated increased urinary mtDNA concentration. The baseline UmtDNA levels were elevated in SICU patients especially in AKI patients, compared with that in healthy controls. UmtDNA Tc number inversely correlated with serum creatine and urinary neutrophil gelatinase-associated lipocalin and directly with estimated glomerular filtration rate. Furthermore, baseline UmtDNA levels had high effectiveness in predicting development of AKI, initiation of RRT, and hospital mortality. Elevated UmtDNA levels could identify newly developed AKI and predict RRT or hospital mortality in SICU patients. UmtDNA Tc number correlated with markers of renal injury and dysfunction, suggesting the involvement of mitochondrial injury in kidney damage among surgical critical illness patients.

Monocyte subsets and monocyte-platelet aggregates: implications in predicting septic mortality among surgical critical illness patients

Background: Monocyte subsets and monocyte–platelet aggregates (MPAs) play important roles in inflammation. Aim: To evaluate the association between the three human monocyte subsets and their contributions to MPAs and mortality among septic patients. Methods: Consecutive septic patients were enrolled in. Age- and gender-matched nonseptic patients were recruited as control patients. Monocyte subsets and monocyte–platelet aggregates were determined by flow cytometric analysis. Results: Elevated percentage of MPAs (MPAs%) was associated with an increased risk of mortality. Conclusions: This study demonstrated increased MPAs% enables the identification of a group of septic patients at high risk of death.

Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later.

IntroductionFor decades, clinicians dealing with immunocompromised and critically ill patients have perceived a link between Candida colonization and subsequent infection. However, the pathophysiological progression from colonization to infection was clearly established only through the formal description of the colonization index (CI) in critically ill patients. Unfortunately, the literature reflects intense confusion about the pathophysiology of invasive candidiasis and specific associated risk factors.MethodsWe review the contribution of the CI in the field of Candida infection and its development in the 20 years following its original description in 1994. The development of the CI enabled an improved understanding of the pathogenesis of invasive candidiasis and the use of targeted empirical antifungal therapy in subgroups of patients at increased risk for infection.ResultsThe recognition of specific characteristics among underlying conditions, such as neutropenia, solid organ transplantation, and surgical and nonsurgical critical illness, has enabled the description of distinct epidemiological patterns in the development of invasive candidiasis.ConclusionsDespite its limited bedside practicality and before confirmation of potentially more accurate predictors, such as specific biomarkers, the CI remains an important way to characterize the dynamics of colonization, which increases early in patients who develop invasive candidiasis.

Plasma metabolomic profiles associated with hospital mortality in surgical critical illness (248.2)

Background: Plasma metabolomic profiling provides an opportunity for discovery‐based studies on human metabolism during illness. We sought to define metabolites that differ between intensive care unit (ICU) patients that did or did not survive hospitalization.Methods: Subjects matched on demographics and nutrient administration in a RCT on glutamine supplementation in surgical ICU patients were selected based on hospital mortality. Serial plasma was analyzed using high‐resolution LC‐MS methods. False discovery rate (FDR; q=0.05) and hierarchal cluster analysis was used to distinguish accurate mass ions (metabolites) significantly different between groups. The METLIN Metabolite Database was used to match ions to known metabolites.Results: A total of 22,305 metabolites were detected (54, 5, 33, and 113 were significantly different between the two groups at days 0, 3, 7, and 14, respectively). Survivors and non‐survivors were differentiated at both day 0 and day 14 by 3 metabolite matches (2 unknowns and stearic acid), and by several others at days 7 and 14 (2 unknowns, terpenoids, drug metabolites). Several drug metabolite matches were higher and several endogenous metabolites were lower in non‐survivors, respectively.Conclusion: High‐resolution LC‐MS can identify plasma metabolomic profiles associated with hospital mortality in adults with surgical critical illness.Grant Funding Source: Supported by grants from the National Institutes of Health Fogarty grants D43 TW007124

Development and preliminary evaluation of a telephone-based mindfulness training intervention for survivors of critical illness.

Persistent symptoms of psychological distress represent an unmet need among intensive care unit (ICU) survivors. We aimed to develop and pilot test a simple telephone-based mindfulness training intervention to address this population's unique needs. Open trial involving survivors of medical and surgical critical illness and their informal caregivers, using a pretest-posttest design. We developed a six-session, telephone-delivered, ICU survivor-specific mindfulness intervention based on past focus groups, the medical literature, and the precedent of the most effective components of existing mindfulness programs. A total of 11 survivors of mechanical ventilation were enrolled, together with 2 informal caregivers for exploratory purposes. Three patients dropped out before intervention initiation because of progressive illness or severe social stressors. Of the 10 remaining participants, 8 (80%) completed the program within 7 weeks. Among these eight patients and caregivers who completed all study procedures, six (75%) experienced improvement in symptoms of psychological distress (anxiety, depression, or post-traumatic stress disorder). Changes in distress symptoms were correlated with improvement in mindfulness qualities, adaptive coping, and emotion regulation. Participants reported high satisfaction with the program in postintervention interviews. A new ICU survivor-specific mindfulness training intervention delivered by telephone was acceptable and feasible. Changes in symptoms of distress were correlated with changes in skills that were targeted by the mindfulness program. Controlled trials are needed to further evaluate this promising intervention.

Heparin-Induced Thrombocytopenia in Medical Surgical Critical Illness

In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to a lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (five vs 12 patients, P = .14), which was statistically significant (three vs 12 patients, P = .046) in a prespecified per-protocol analysis that excluded patients with DVT at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis may reduce HIT frequency in patients in the ICU. In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to the study drug and other open-label heparin, to determine whether the study drug plausibly explained seroconversion to SRA+ status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT. HIT-associated thrombosis occurred in 10 of 17 patients (58.8%) (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events (P = .020), including less seroconversion (P = .058) and less breakthrough of thrombocytopenia/thrombosis (P = .032). Antiplatelet factor 4/heparin IgG antibodies by enzyme-linked immunosorbent assay were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%, P &lt; .001). One patient with HIT-associated DVT died after UFH bolus (anaphylactoid reaction), whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeutic-dose UFH. The lower risk of HIT in patients in the ICU receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.

Programmed Death 1 Expression as a Marker for Immune and Physiological Dysfunction in the Critically Ill Surgical Patient

Programmed death 1 (PD-1) is an inhibitor protein receptor for the immune system and has been shown to be upregulated in animal models of critical illness as well as after trauma and in burn victims in humans. It is believed that PD-1 may play a role in the immune dysfunction seen in surgical critical illness. However, although prior studies have associated changes in PD-1 expression with altered immune cell function, it is not known if a correlation with clinical status exists. We therefore aimed to describe a potential role for PD-1 in the immune dysfunction seen in critically ill trauma and surgical patients. This is an observational cohort study. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated on critically ill and injured trauma and surgical intensive care unit patients from a tertiary care/level I trauma center. Blood was drawn within 24 h of establishment of diagnosis and admission to the intensive care unit to measure circulating cytokine levels, as well as PD-1 expression on circulating cells. Main outcome measures included PD-1 expression on leukocytes and the relationship to physiological dysfunction (APACHE II) as well as the correlation of PD-1 expression and interleukin 10 levels among patients with severe physiological dysfunction. Samples were collected from 90 critically ill surgical patients. Among patients with severe physiological dysfunction (APACHE II >20), there were increased numbers of granulocytes (median, 144 vs. 90 cells/μL; P = 0.037) and monocytes (median, 12 vs. 6 cells/μL; P = 0.022) with PD-1 expression. In addition, among patients with an APACHE II score of greater than 20, there was a larger percentage of CD3 cells (44% vs. 29%; P = 0.015) expressing PD-1. When only patients with an APACHE II score greater than 20 were assessed, PD-1 expression on monocytes correlated positively with interleukin levels in the serum (r = 0.525, P = 0.05). Variability in the expression of PD-1 on leukocytes in critical surgical illness correlates with physiological dysfunction and suggests that PD-1 may be a valuable tool in the assessment of immune dysfunction following trauma or severe surgical insult.

Nurse-Perceived Barriers to Effective Communication Regarding Prognosis and Optimal End-of-Life Care for Surgical ICU Patients: A Qualitative Exploration

Integration of palliative care for intensive care unit (ICU) patients is important but often challenging, especially in surgical ICUs (SICUs), in part because many surgeons equate palliative care with terminal care and failure of restorative care. SICU nurses, who are key front-line clinicians, can provide insights into barriers for delivery of optimal palliative care in their setting. We developed a focus group guide to identify barriers to two key components of palliative care-optimal communication regarding prognosis and optimal end-of-life care-and used the tool to conduct focus groups of nurses providing bedside care in three SICUs at a tertiary care, academic, inner city hospital. Using content analysis technique, responses were organized into thematic domains that were validated by independent observers and a subset of participating nurses. Four focus groups included a total of 32 SICU nurses. They identified 34 barriers to optimal communication regarding prognosis, which were summarized into four domains: logistics, clinician discomfort with discussing prognosis, inadequate skill and training, and fear of conflict. For optimal end-of-life care, the groups identified 24 barriers in four domains: logistics, inability to acknowledge an end-of-life situation, inadequate skill and training, and cultural differences relating to end-of-life care. Nurses providing bedside care in SICUs identify barriers in several domains that may impede optimal discussions of prognoses and end-of-life care for patients with surgical critical illness. Consideration of these perceived barriers and the underlying SICU culture is relevant for designing interventions to improve palliative care in this setting.

Efficacy of Therapy with Recombinant Human Activated Protein C of Critically Ill Surgical Patients with Infection Complicated by Septic Shock and Multiple Organ Dysfunction Syndrome

Septic shock causing or complicating critical surgical illness results in high mortality. Drotrecogin alfa (activated), known also as recombinant human activated protein C (rhAPC) has become controversial as therapy, owing to persisting questions of efficacy and safety. We hypothesized rhAPC to be effective therapy for critically ill surgical patients with septic shock. Open-label therapy with rhAPC (by predefined criteria) of 108 critically ill surgical patients. Treated patients were matched individually in prospect for age, gender, Acute Physiology and Chronic Health Evaluation (APACHE)-II and -III scores, site of infection, and organism (0-2 points each, maximum 12 points) with 108 patients from our 15,000-patient surgical intensive care unit database who did not receive rhAPC. No match was accepted if <6 points. Multiple organ dysfunction (MOD) scores and data regarding cortisol concentrations, bleeding complications, and transfusion requirements were collected. The primary endpoint was 28-day mortality, with mortality for hospitalization and resolution of organ dysfunction as secondary endpoints. Statistical analyses included ANOVA, c statistic, binary logistic regression, and Kaplan-Meier time-to-event and Cox proportional hazards analyses; α=0.05. The mean match score was 9.2±0.1 points (range, 6-12 points). Patients were well matched by all criteria, including baseline MOD score (9.5±0.7 vs. 9.8±0.3 points, p=0.66). Mean age was 68.1±1.1 years (p=0.49), Mean APACHE-III score was 99.6±1.5 points (p=0.87). Mean time to rhAPC administration was 25±3 h. Survival at 28 days after rhAPC was 71.3% vs. 49.1% (p=0.001); hospital survival was 57.4% vs. 40.7% (p=0.02). By logistic regression, rhAPC therapy resulted in improved 28-day survival (OR 2.57, 95% CI 1.46-4.52, p=0.001) (model χ2 11.244, p=0.001); and hospital survival (OR 1.96, 95% CI 1.14-3.36, p=0.015) (model χ2 6.03, p=0.014). The MOD score decreased significantly (p=0.012) during rhAPC therapy. Therapy with rhAPC appeared to improve survival in surgical ICU patients with life-threatening infection characterized by septic shock and organ dysfunction.

Long-term Survival After Surgical Critical Illness

To identify the prognostic importance of preceding invasive ventilation, renal replacement therapy, and catecholamine therapy for long-term survivors after surgical critical illness. Nothing is known about the effect of preceding intensive care unit (ICU)-related therapies on long-term outcome. We performed a retrospective analysis of prospectively collected data of an ICU patient cohort linked to a local database. Adult patients (n = 1462) admitted to a 12-bed ICU between 1993 and 2005, who had an ICU length of stay of more than 4 days, were followed up until the end of the second year after ICU admission. Hazard function was explored by Weibull modeling and likelihood ratio tests. Cox-type structured hazard regression models were used to analyze linear, nonlinear, or time-varying associations of therapeutic variables with 2-year survival time of a patient subgroup, which had survived the period of high hazard. Hazard rate declined exponentially up to day 195 after ICU admission, and became constant thereafter. A total of 808 patients reached this stable stage of their disease forming the study population. Of these patients, 648 (80.2%) were still alive at the end of the second year after ICU admission. Underlying diseases were major determinants for long-term outcome. Long-term mortality was significantly associated with the acute extent of physiological derangement during ICU stay (maximum Apache II score), but was independent from the duration of preceding invasive organ support. In surgical patients with a prolonged ICU length of stay, an exorbitant mortality exists for about half a year after ICU admission. Later on, life expectancy of surviving patients is largely determined by the underlying disease and, to a minor degree, by the acute extent of homeostatic disturbance during ICU stay. The duration of preceding invasive therapies does not limit long-term survival.

Severe hypocholesterolemia in surgical patients, sepsis, and critical illness

After surgery, in sepsis and various critical illnesses, factors such as severity of the acute phase response, liver dysfunction, and hemodilution from blood loss have cumulative impacts in decreasing cholesterol; therefore, degree of hypocholesterolemia often reflects severity of illness. The direct correlation between cholesterol and several plasma proteins is mediated by the parallel impact of commonly shared determinants. Cholestasis is associated with a moderation of the degree of hypocholesterolemia. In human sepsis, the poor implications of hypocholesterolemia seem to be aggravated by the simultaneous development of hypertriglyceridemia. Cholesterol and triglyceride levels reflect altered lipoprotein patterns, and the issue is too complex and too poorly understood to be reduced to simple concepts; nevertheless, these simple measurements often represent helpful adjunctive clinical tools.

Multiple Organ Dysfunction Syndrome in Critical Surgical Illness

Multiple organ dysfunction syndrome (MODS) is the leading cause of death in surgical patients and in trauma patients who survive the first 24 h. First observed systematically among Vietnam War-era battle casualties who began to survive previously fatal injuries owing to improved evacuation, triage, and resuscitation, only to develop catastrophic manifestations of organ failure never before seen, the syndrome was recognized formally in 1975 as "multiple organ failure." Ensuing observations and investigations, undertaken in large part by surgeon-scientists, have refined our current understanding of MODS, yielding better outcomes. Review and synthesis of pertinent literature with personal observations and recollections of the senior investigator. The MODS is now recognized as a continuum of physiologic derangements, rather than an all-or-nothing phenomenon. The most common precipitant appears to be ischemia-reperfusion injury, although severe sepsis also is commonplace. Descriptive biology has enhanced the understanding of the pathogenesis and outcomes of MODS, although the therapy is largely supportive, making prevention of paramount importance. Measures such as drotrecogin alfa (activated), intensive insulin therapy, corticosteroids, and low tidal volume ventilation may be effective. Although current treatment of MODS remains primarily supportive, the mortality rate appears to be decreasing. Appreciation of the interrelations between the inflammatory and coagulation systems provides hope in the battle against this frequent, elusive, deadly, and costly syndrome.

Characteristics of hemoglobin changes and its significance in critically ill patients

To investigate characteristics of hemoglobin changes in surgical critically ill patients. One hundred and ten consecutive critically ill patients admitted to the surgical ICU of Shanghai Ruijin Hospital were prospectively included in the clinical trial from January 2004 to December 2006. And changes of hemoglobin and prognosis were retrospectively analyzed. The inclusion criteria were surgical critical illness, APACHE II > or = 8 points, and admission to ICU within 48 hours after onset of critical illness, except for patients with bleeding. According to hemoglobin level before transfusion, 110 patients divide into the low level hemoglobin group (< or = 100 g/L) and the high level hemoglobin group (> 100 g/L). Time interval for valley value of hemoglobin within 28 days and incidence of hypo-hemoglobin (< or = 100 g/L) were investigated; the mean hemoglobin level, mean APACHE II scores, amount of concentrated red blood cells and rate of mechanical ventilation as well as duration of ventilation within 28 days were calculated. ICU survival rate was observed. Level of hemoglobin in low level group was decreased significantly compared to high level group [(86.3 +/- 23.8) g/L vs. (112.9 +/- 20.4) g/L, P < 0.01]; and time of its valley values was shorter than that of high level group [(3 +/- 1) d vs. (5 +/- 2) d, P < 0.01]; the responding level of hemoglobin was (89.3 +/- 11.3) g/L and (110.0 +/- 12.5) g/L (P = 0.001), respectively. Incidence of hypo-hemoglobin was 92.9% in low level group and 0 in high level group within 28 days (P < 0.01). Hemoglobin level of high level group was significantly higher than that of low level group within 28 days [(120.2 +/- 12.5) g/L vs. (89.3 +/- 11.3) g/L, P < 0.05], and the total amount of blood transfusion in high level group was less significantly than that of low level group [(12.4 +/- 10.1) U vs. (24.0 +/- 15.6) U, P = 0.042]; mean APACHE II score in high level group was significantly lower than that of low level group [(8.7 +/- 2.4) vs. (13.2 +/- 4.3), P < 0.001]; rate of mechanical ventilation was no difference (56.4% vs. 52.7%, P = 0.765); but duration of mechanical ventilation was shorter than that of low level group [(12 +/- 5) d vs. (25 +/- 7) d, P < 0.001]. Survival rate in high level group in ICU was significantly higher than that of low level group (80.0% vs. 61.8%, P = 0.036). Prolonged hypo-hemoglobin level (< or = 100 g/L) and valley value in advance suggest bad prognosis.

Randomized, Double-Blind, Placebo-Controlled Trial of Effects of Enteral Iron Supplementation on Anemia and Risk of Infection during Surgical Critical Illness

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. 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. 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). 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).

Decreasing Magnitude of Multiple Organ Dysfunction Syndrome Despite Increasingly Severe Critical Surgical Illness: A 17-Year Longitudinal Study

Multiple organ dysfunction syndrome (MODS) remains prevalent and the leading cause of mortality in the surgical intensive care unit (ICU). Improvements in ICU care in the last 10 years (e.g., tight glycemic control, activated protein C, fewer transfusions causing fewer nosocomial infections) may have decreased the incidence, magnitude, and mortality of MODS, as hypothesized in this study. Longitudinal 17-year prospective study of 11,314 ICU patients (academic/tertiary unit, Level I trauma center), 5,157 (45.5%) of whom developed any degree of MODS (Marshall score, cumulative). Data collected included Admission Acute Physiology and Chronic Health Evaluation (APACHE)-II and APACHE-III scores, MOD score (MODsc), hospital mortality, and the incidence and magnitude of MODS. The ratio of MODsc: APACHE III was calculated. Analyses (X +/- SEM, chi2, repeated-measures ANOVA, linear and polynomial regression, c-statistic) were performed for calendar-year intervals beginning in 1990 through 2006. Among MODS patients, the mean MODsc was 6.3 +/- 0.1 points, and the mortality rate was 22%. The APACHE III score increased significantly (p < 0.0001) over time, but the mortality rate was unchanged (r2 = 0.02). Adjusted for illness severity (MODsc:A3), the magnitude of MODS decreased significantly (p < 0.0001) during the time period. Despite significant increases in admission APACHE III score over 17 years, the adjusted magnitude of MODS (MODsc:A3) decreased. Given the strong association between MODS and mortality for critically ill surgical patients, it is likely that the unchanged risk-adjusted mortality observed over time is due to the reduced magnitude of MODS.