Prospective evaluation of intravascular volume status in critically ill patients: does inferior vena cava collapsibility correlate with central venous pressure?

BACKGROUND: In search of a standardized noninvasive assessment of intravascular volume status, we prospectively compared the sonographic inferior vena cava collapsibility index (IVC-CI) and central venous pressures (CVPs). Our goals included the determination of CVP behavior across clinically relevant IVC-CI ranges, examination of unitary behavior of IVC-CI with changes in CVP, and estimation of the effect of positive end-expiratory pressure (PEEP) on the IVC-CI/CVP relationship. METHODS: Prospective, observational study was performed in surgical/medical intensive care unit patients between October 2009 and July 2013. Patients underwent repeated sonographic evaluations of IVC-CI. Demographics, illness severity, ventilatory support, CVP, and patient positioning were recorded. Correlations were made between CVP groupings (<7, 7-12, 12-18, 19+) and IVC-CI ranges (<25, 25-49, 50-74, 75+). Comparison of CVP (2-unit quanta) and IVC-CI (5-unit quanta) was performed, followed by assessment of per-unit ΔIVC-CI/ΔCVP behavior as well as examination of the effect of PEEP on the IVC-CI/CVP relationship. RESULTS: We analyzed 320 IVC-CI/CVP measurement pairs from 79 patients (mean [SD] age, 55.8 [16.8] years; 64.6% male; mean [SD] Acute Physiology and Chronic Health Evaluation II, 11.7 [6.21]). Continuous data for IVC-CI/CVP correlated poorly (R = 0.177, p < 0.01) and were inversely proportional, with CVP less than 7 noted in approximately 10% of the patients for IVC-CIs less than 25% and CVP less than 7 observed in approximately 85% of patients for IVC-CIs greater than or equal to 75%. Median ΔIVC-CI per unit CVP was 3.25%. Most measurements (361 of 320) were collected in mechanically ventilated patients (mean [SD] PEEP, 7.76 [4.11] cm H2O). PEEP-related CVP increase was approximately 2 mm Hg to 2.5 mm Hg for IVC-CIs greater than 60% and approximately 3 mm Hg to 3.5 mm Hg for IVC-CIs less than 30%. PEEP also resulted in lower IVC-CIs at low CVPs, which reversed with increasing CVPs. When IVC-CI was examined across increasing PEEP ranges, we noted an inverse relationship between the two variables, but this failed to reach statistical significance. CONCLUSION: IVC-CI and CVP correlate inversely, with each 1 mm Hg of CVP corresponding to 3.3% median ΔIVC-CI. Low IVC-CI (<25%) is consistent with euvolemia/hypervolemia, while IVC-CI greater than 75% suggests intravascular volume depletion. The presence of PEEP results in 2 mm Hg to 3.5 mm Hg of CVP increase across the IVC-CI spectrum and lower collapsibility at low CVPs. Although IVC-CI decreased with increasing degrees of PEEP, this failed to reach statistical significance. While this study represents a step forward in the area of intravascular volume estimation using IVC-CI, our findings must be applied with caution owing to some methodologic limitations. LEVEL OF EVIDENCE: Diagnostic study, level III. Prognostic study, level III.

Red blood cell transfusion is associated with decreased in-hospital muscle strength among critically ill patients requiring mechanical ventilation.

PURPOSE: Red blood cell (RBC) transfusion is linked to poor functional recovery after surgery and trauma. To investigate one potential mechanism, we examined the association between RBC transfusion and muscle strength in a cohort of critically ill patients. METHODS: We performed a secondary analysis of 124 critically ill, mechanically ventilated patients enrolled in 2 prospective cohort studies where muscle strength testing was performed at a median of 12 days after mechanical ventilation onset. We examined the association between RBC transfusion and dynamometry handgrip strength using multivariable linear regression, adjusting for study site, age, sex, Acute Physiology and Chronic Health Evaluation, Sequential Organ Failure Assessment score, days from hospital admission to examination, and steroid use. Secondary outcomes included systematic manual muscle strength and intensive care unit-acquired paresis. RESULTS: Among 124 subjects, 73 (59%) received RBC transfusion in the 30 days before examination. In adjusted analyses, RBC transfusion was significantly associated with weaker handgrip (adjusted mean difference, -9.9 kg; 95% confidence interval, -16.6 to -3.2; P < .01) and proximal manual muscle strength (adjusted mean difference in Medical Research Council score, -0.5; 95% confidence interval, -0.7 to -0.2; P < .01) but not intensive care unit-acquired paresis. CONCLUSIONS: Red blood cell transfusion was associated with decreased muscle strength in this cohort of critically ill patients after adjusting for illness severity and organ dysfunction. Further studies are needed to validate these results and probe mechanisms.

Thrombospondin-1 contributes to mortality in murine sepsis through effects on innate immunity.

BACKGROUND: Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFß1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS: We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFß1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS: TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFß1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition.

Results from the National Sepsis Practice Survey: use of drotrecogin α (activated) and other therapeutic decisions.

PURPOSE: We sought to evaluate factors associated with choices about provided care for patients with septic shock, including the use of drotrecogin α (activated) (DAA). MATERIALS AND METHODS: We administered a mail-based survey to a random sample of intensivists. Study vignettes presented patients with septic shock with identical severity of illness scores but different ages, body mass indices, and comorbidities. Respondents estimated outcomes and selected care beyond standardized initial care (eg, antibiotics) for each hypothetical patient. RESULTS: For most vignettes (99.1%), respondents added care, most commonly low tidal volume ventilation (87.6%) and enteral nutrition (73.3%). Choosing to administer DAA was not associated with predictions about mortality or bleeding. Vignettes with early-stage lung cancer were less likely to receive DAA. Time since medical school graduation was also associated with lower odds of selecting DAA. Most respondents (52.6%) chose identical care for all 4 completed vignettes. CONCLUSIONS: There was wide variability in the therapeutic choices of respondents. The use of DAA was not associated with perceived risk of mortality or bleeding, as recommended by consensus guidelines. Physicians appear to base treatment decisions in septic shock on a consistent pattern of practice rather than estimates of patient outcome.

Results from the national sepsis practice survey: predictions about mortality and morbidity and recommendations for limitation of care orders.

INTRODUCTION: Critically ill patients and families rely upon physicians to provide estimates of prognosis and recommendations for care. Little is known about patient and clinician factors which influence these predictions. The association between these predictions and recommendations for continued aggressive care is also understudied. METHODS: We administered a mail-based survey with simulated clinical vignettes to a random sample of the Critical Care Assembly of the American Thoracic Society. Vignettes represented a patient with septic shock with multi-organ failure with identical APACHE II scores and sepsis-associated organ failures. Vignettes varied by age (50 or 70 years old), body mass index (BMI) (normal or obese) and co-morbidities (none or recently diagnosed stage IIA lung cancer). All subjects received the vignettes with the highest and lowest mortality predictions from pilot testing and two additional, randomly selected vignettes. Respondents estimated outcomes and selected care for each hypothetical patient. RESULTS: Despite identical severity of illness, the range of estimates for hospital mortality (5th to 95th percentile range, 17% to 78%) and for problems with self-care (5th to 95th percentile range, 2% to 74%) was wide. Similar variation was observed when clinical factors (age, BMI, and co-morbidities) were identical. Estimates of hospital mortality and problems with self-care among survivors were significantly higher in vignettes with obese BMIs (4.3% and 5.3% higher, respectively), older age (8.2% and 11.6% higher, respectively), and cancer diagnosis (5.9% and 6.9% higher, respectively). Higher estimates of mortality (adjusted odds ratio 1.29 per 10% increase in predicted mortality), perceived problems with self-care (adjusted odds ratio 1.26 per 10% increase in predicted problems with self-care), and early-stage lung cancer (adjusted odds ratio 5.82) were independently associated with recommendations to limit care. CONCLUSIONS: The studied clinical factors were consistently associated with poorer outcome predictions but did not explain the variation in prognoses offered by experienced physicians. These observations raise concern that provided information and the resulting decisions about continued aggressive care may be influenced by individual physician perception. To provide more reliable and accurate estimates of outcomes, tools are needed which incorporate patient characteristics and preferences with physician predictions and practices.

Latency associated peptide has in vitro and in vivo immune effects independent of TGF-beta1.

Latency Associated Peptide (LAP) binds TGF-beta1, forming a latent complex. Currently, LAP is presumed to function only as a sequestering agent for active TGF-beta1. Previous work shows that LAP can induce epithelial cell migration, but effects on leukocytes have not been reported. Because of the multiplicity of immunologic processes in which TGF-beta1 plays a role, we hypothesized that LAP could function independently to modulate immune responses. In separate experiments we found that LAP promoted chemotaxis of human monocytes and blocked inflammation in vivo in a murine model of the delayed-type hypersensitivity response (DTHR). These effects did not involve TGF-beta1 activity. Further studies revealed that disruption of specific LAP-thrombospondin-1 (TSP-1) interactions prevented LAP-induced responses. The effect of LAP on DTH inhibition depended on IL-10. These data support a novel role for LAP in regulating monocyte trafficking and immune modulation.

Hyperglycemia in patients with acute myeloid leukemia is associated with increased hospital mortality.

BACKGROUND: Hyperglycemia is often observed in medically ill patients. Previous studies have shown that patients with hyperglycemia during induction therapy for acute lymphoblastic leukemia develop more infections and have shorter disease-free survival. The authors hypothesized that hyperglycemia may be associated with adverse outcomes in patients with acute myeloid leukemia (AML) and sought to determine whether this association exists in this population. METHODS: The authors performed a retrospective cohort study to examine the relation between hyperglycemia and hospital mortality in patients with the diagnosis of AML. Two hundred eighty-three adult patients were treated over a 3-year period. All hospitalizations were reviewed during the study period, and glucose exposure and outcomes were quantified. RESULTS: Hyperglycemia during a patient's hospitalization was associated with increased hospital mortality (OR, 1.38; 95% CI, 1.23-1.55; P < .001) after adjusting for covariates, including disease state, treatment type, and response. The rise in mortality was evident at even mild levels (110-150 mg/dL) of glucose elevation. Although the odds of developing severe sepsis (OR, 1.24; 95% CI, 1.13.-1.38; P < .001) or severe sepsis with respiratory failure (OR, 2.04; 95% CI, 1.44-2.91; P < .001) were increased with hyperglycemia, sepsis did not appear to be the main factor responsible for the negative impact of hyperglycemia on hospital mortality. CONCLUSIONS: This study demonstrated an association between hospital mortality and even modest levels of hyperglycemia in AML patients. Prospective studies are needed to confirm this association and to discern causal pathways that mediate this effect.

Specificity of computerized physician order entry has a significant effect on the efficiency of workflow for critically ill patients.

BACKGROUND: Critically ill patients require rapid care, yet they are also at risk for morbidity from the potential complications of that care. Computerized physician order entry (CPOE) is advocated as a tool to reduce medical errors, improve the efficiency of healthcare delivery, and improve outcomes. Little is known regarding the essential attributes of CPOE in the intensive care unit (ICU). OBJECTIVE: To assess the effect of CPOE on ICU patient care. DESIGN: Retrospective before and after cohort study. SETTING: An academic ICU. PATIENTS: Patients admitted to the ICU during use of the initial CPOE application and those admitted after its modification. INTERVENTIONS: Comprehensive order interface redesign improving clarity, specificity, and efficiency. MEASUREMENTS: Orders for complex ICU care were compared between the two groups. In addition, the use of higher-efficiency CPOE order paths was tracked. RESULTS: Patients treated with both the initial and modified CPOE system were similar for all measured characteristics. With the modified CPOE system, there were significant reductions in orders for vasoactive infusions, sedative infusions, and ventilator management. There was also a significant increase in orders executed through ICU-specific order sets after system modifications. LIMITATIONS: This retrospective study cannot assess issues related to learner expertise and is meant to only suggest the importance of developing CPOE systems that are appropriate for specialty care environments. CONCLUSION: Appropriate CPOE applications can improve the efficiency of care for critically ill patients. The workflow requirements of individual units must be analyzed before technologies like CPOE can be properly developed and implemented.