Overtreatment of Heparin-Induced Thrombocytopenia in the Surgical ICU.

OBJECTIVE: Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated. DESIGN: In this clinical prospective study, data were collected including age, sex, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts scores. Heparin-induced thrombocytopenia-positive patients were defined as those with both positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay (optical density, ≥ 0.40) and positive serotonin release assay results. SETTING: Urban tertiary medical center. PATIENTS: Patients admitted to the surgical and cardiac ICU who were presumed to have heparin-induced thrombocytopenia and underwent antiplatelet factor 4/heparin enzyme-linked immunosorbent assay and serotonin release assay testing between January 1, 2011, and August 1, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 135 patients had 4Ts, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, and serotonin release assay scores. A total of 11 patients (8.1%) had positive serotonin release assay and 80 patients had positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay; 10 patients were identified as heparin-induced thrombocytopenia positive. Positive serotonin release assay was noted in nine of 11 patients (81.8%) with antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density greater than or equal to 2.0, compared with one of 22 patients (4.5%) with optical density values of 0.85-1.99, and one of 102 patients (1.0%) with optical density values of 0-0.84. Out of 135 patients, 29 patients (21.5%) received treatment with argatroban, lepirudin, or fondaparinux: 10 of 10 heparin-induced thrombocytopenia-positive patients (100%) compared with 19 of 125 heparin-induced thrombocytopenia-negative patients (15%). CONCLUSIONS: Overtreatment of heparin-induced thrombocytopenia in the surgical ICU continues even with recent increased caution encouraging a higher antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density threshold before initiating treatment. More stringent criteria should be used to determine when to order serologic testing and when the results of such testing should prompt a change in anticoagulant treatment. If antiplatelet factor 4/heparin enzyme-linked immunosorbent assay is used to consider immediate treatment, an optical density greater than or equal to 2.0 may be a more appropriate threshold.

High-value care in the surgical intensive care unit: effect on ancillary resources.

BACKGROUND: Changes in health care policies have influenced transformations in hospital systems to be cost-efficient while maintaining robust outcomes. This is particularly important in intensive care units where significant resources are used to care for critically ill patients. We sought to determine whether high-value care processes (HVCp) implemented in a surgical intensive care unit (SICU) have an impact on commonly used ancillary tests. MATERIALS AND METHODS: An implementation phase using a Lean Six Sigma approach was performed in October 2014 at a 24-bed large academic center SICU with aims to decrease orders of excessive daily laboratory tests and X-rays. The HVCp implemented included use of daily checklists, staff education, and visual reminders emphasizing the importance of appropriate laboratory tests and chest X-rays. Preintervention (July 2014-October 2014) and post-intervention (November 2014-June 2015) phases were compared. RESULTS: Average SICU census, case mix index (4.3 versus 4.4, P = 0.57), all patient refined severity of illness (3.2 versus 3.2, P = 0.91), and SICU mortality (7.1% versus 5.1%, P = 0.18) were similar in both phases. A significant reduction of excessive laboratory tests was evident after the implementation period. Eight hundred sixty-five arterial blood gases/mo were obtained in the preintervention phase compared with 420 arterial blood gases/mo after intervention (P = 0.004), representing a 51.4% reduction. Similar results were obtained with complete blood counts, basic metabolic profiles, coagulation profiles, and chest X-rays (12%, 17.8%, 30.2%, and 20.3% reductions, respectively), a total estimated cost savings of $59,137/mo and prevention of excess phlebotomy of approximately 4 L of blood/mo. CONCLUSIONS: By implementing an HVCp including a checklist, visual reminders, and provider education, we significantly reduced the use of commonly ordered ancillary tests in the SICU without affecting outcomes, resulting in an annual cost savings of $710,000.

Prospective evaluation of early propranolol after traumatic brain injury.

BACKGROUND: Although beta-adrenergic receptor blockade may improve outcomes after traumatic brain injury (TBI), its early use is not routine. We hypothesize that judicious early low-dose propranolol after TBI (EPAT) will improve outcomes without altering bradycardia or hypotensive events. METHODS: We conducted a prospective, observational study on all patients who presented with moderate-to-severe TBI from March 2010-August 2013. Ten initial patients did not receive propranolol (control). Subsequent patients received propranolol at 1-mg intravenous every 6 h starting within 12 h of intensive care unit (ICU) admission (EPAT) for a minimum of 48 h. Heart rate and blood pressure were recorded hourly for the first 72 h. Bradycardia and hypotensive events, mortality, and length of stay (LOS) were compared between cohorts to determine significant differences. RESULTS: Thirty-eight patients were enrolled; 10 control and 28 EPAT. The two cohorts were similar when compared by gender, emergency department (ED) systolic blood pressure, ED heart rate, and mortality. ED Glasgow coma scale was lower (4.2 versus 10.7, P < 0.01) and injury severity score higher in control. EPAT patients received a mean of 10 ± 14 doses of propranolol. Hypotensive events were similar between cohorts, whereas bradycardia events were higher in control (5.8 versus 1.6, P = 0.05). ICU LOS (15.4 versus 30.4 d, P = 0.02) and hospital LOS (10 versus 19.1 d, P = 0.05) were lower in EPAT. Mortality rates were similar between groups (10% versus 10.7%, P = 0.9). The administration of propranolol led to no recorded complications. CONCLUSIONS: Although bradycardia and hypotensive events occur early after TBI, low-dose intravenous propranolol does not increase their number or severity. Early use of propranolol after TBI appears to be safe and may be associated with decreased ICU and hospital LOS.

Body mass index strongly impacts the diagnosis and incidence of heparin-induced thrombocytopenia in the surgical intensive care unit.

BACKGROUND: The obese state has been linked to several immune-mediated conditions. Our objective was to examine the association of body mass index (BMI) with the diagnosis of heparin-induced thrombocytopenia (HIT). METHODS: Prospectively collected data on patients in the surgical and cardiac intensive care unit suspected of having HIT between January 2007 and August 2014 were analyzed. Patients were categorized into five discrete BMI (kg/m) groups and compared. Data collected included Warkentin 4-T scores, antiplatelet factor 4 (anti-PF4OD) values, serotonin release assay values, and thromboembolic diseases. HIT positivity was defined as serotonin release assay value greater than 20%. RESULTS: Of 304 patients meeting inclusion criteria, mean (SD) age was 62.1 (16.5) years, 59% were male, and mean (SD) BMI was 27 (6) kg/m. Thirty-six (12%) were positive for HIT. Incidence of HIT increased progressively with BMI (0%, 8%, 11%, 19%, 36%; p < 0.001). Compared with patients with normal BMI, patients with a BMI of 30 kg/m to 39.9 kg/m had a 200% increase in the odds for HIT (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.20-7.54; p = 0.019), while patients with a BMI of 40 kg/m or greater had a 600% increase (OR, 6.98; 95% CI, 1.59-28.2; p = 0.012). After regression analysis, BMI remained an independent predictor of the development of HIT (adjusted OR per kg/m, 1.08; 95% CI, 1.02-1.14; p = 0.010). Anti-PF4OD values greater than or equal to 2.0 also increased with BMI (p < 0.001). In-hospital mortality increased significantly with BMI above normal (p = 0.026). Warkentin 4-T scores, deep venous thrombosis, pulmonary embolism, and stroke incidence did not correlate with changes in BMI. CONCLUSION: Increasing BMI seems to be strongly associated with increased rates of HIT in intensive care unit patients. Obesity is an important new clinical variable for estimating the pretest probability of HIT, and patient "thickness" could be considered a fifth "T" of the 4-T scoring system. Additional biochemical work is indicated to decipher the role of obesity in this immune-mediated condition. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

CT Chest with IV Contrast Compared with CT Angiography after Blunt Trauma.

Blunt aortic injury (BAI) after chest trauma is a potentially lethal condition. Rapid diagnosis is important to appropriately treat patients. The purpose of this study was to compare CT with intravenous contrast (CTI) to CT with angiography (CTA) in the initial evaluation of blunt chest trauma patients. This was a retrospective review of all blunt trauma patients who received a CTI or CTA during the initial evaluation at an urban Level I trauma center from January 1, 2010 to December 31, 2013. Two-hundred and eighty-one trauma patients met inclusion criteria. Most, 167/281 (59%) received CTI and 114/281 (41%) received CTA. There were no differences between cohorts in age, gender, initial heart rate, systolic blood pressure, and Glasgow Coma Scale in emergency department. Mortality rates were similar for CTI and CTA (4% vs 8%, P = 0.20). CTI identified an injury in 54 per cent compared with 46 per cent in CTA (P = 0.05). Overall, 2 per cent of patients had BAI with similar rates in CTI and CTA (2% vs 2%, P = 0.80). BAI was not missed using either CTI or CTA. Trauma patients studied with CTI had similar diagnostic findings as CTA. CTI may be preferable to CTA during the initial assessment for possible BAI because of a single contrast injection for whole body CT.

Activation of Massive Transfusion for Elderly Trauma Patients.

Massive transfusion protocol (MTP) is used to resuscitate patients in hemorrhagic shock. Our goal was to review MTP use in the elderly. All trauma patients who required activation of MTP at an urban Level I trauma center from January 1, 2011 to December 31, 2013 were reviewed retrospectively. Elderly was defined as age ≥ 60 years. Sixty-six patients had MTP activated: 52 nonelderly (NE) and 14 elderly (E). There were no statistically significant differences between the two cohorts for gender, injury severity score, head abbreviated injury scale, emergency department Glasgow Coma Scale, initial hematocrit, intensive care unit length of stay, or hospital length of stay. Mean age for NE was 35 years and 73 years for E (P < 0.01). Less than half (43%) of E patients with activation of MTP received 10 or more units of blood products compared with 69 per cent of the NE (P = 0.07). Mortality rates were similar in the NE and the E (53%vs 50%, P = 0.80). After multivariate analysis with Glasgow Coma Scale, injury severity score, and blunt versus penetrating trauma, elderly age was not a predictor of mortality after MTP (P = 0.35). When MTP is activated, survival to discharge in elderly trauma patients is comparable to younger patients.

Selective Nonoperative Management of Abdominal Stab Wounds.

Stab wounds (SW) to the abdomen traditionally require urgent exploration when associated with shock, evisceration, or peritonitis. Hemodynamically stable patients without evisceration may benefit from serial exams even with peritonitis. We compared patients taken directly to the operating room with abdominal SWs (ED-OR) to those admitted for serial exams (ADMIT). We retrospectively reviewed hemodynamically stable patients presenting with any abdominal SW between January 2000 and December 2012. Exclusions included evidence of evisceration, systolic blood pressure ≤110 mm Hg, or blood transfusion. NON-THER was defined as abdominal exploration without identification of intra-abdominal injury requiring repair. Of 142 patients included, 104 were ED-OR and 38 were ADMIT. When ED-OR was compared with ADMIT, abdominal Abbreviated Injury Score was higher (2.4 vs 2.1; P = 0.01) and hospital length of stay was longer (4.8 vs 3.3 days; P = 0.04). Incidence of NON-THER was higher in ED-OR cohort (71% vs 13%; P ≤ 0.001). In a regression model, ED-OR was a predictor of NON-THER (adjusted odds ratio 16.6; P < 0.001). One patient from ED-OR expired after complications from NON-THER. There were no deaths in the ADMIT group. For those patients with abdominal SWs who present with systolic blood pressure ≥110 mm Hg, no blood product transfusion in the emergency department and lacking evisceration, admission for serial abdominal exams may be preferred regardless of abdominal exam.

CT Chest with IV Contrast Compared with CT Angiography after Blunt Trauma.

Blunt aortic injury (BAI) after chest trauma is a potentially lethal condition that requires rapid diagnosis for appropriate treatment. We compared CT with IV contrast (CTI) with CT with angiography (CTA) during the initial phase of care at an urban Level I trauma center from January 1, 2010 to December 31, 2013. Overall, 281 patients met inclusion criteria with 167 (59%) CTI and 114 (41%) CTA. There were no differences between cohorts in age, gender, initial heart rate, systolic blood pressure, and Glasgow Coma Scale. Mortality rates were similar for CTI and CTA (4% vs 8%, P = 0.20). CTI identified any chest injury in 54 per cent of patients compared with 46 per cent with CTA (P = 0.05). The rate of BAI was similar with CTI and CTA (2% vs 2%, P = 0.80), and neither modality was falsely negative. We conclude that CTI and CTA are similar at evaluating trauma patients for BAI, although CTI may be preferable during the initial assessment phase because the contrast injection may be combined with abdominal scanning and image time is reduced when whole-body CT is required.

Abdominal Injuries in the "Found Down": Is Imaging Indicated?

BACKGROUND: We sought to investigate the incidence of abdominal injuries in "found down" trauma patients to better understand the value of emergency department (ED) imaging. Found down patients are at high risk for injuries to the head or neck and low risk to the abdomen or pelvis, so imaging with CT of the abdomen/pelvis (AP) or Focused Assessment with Sonography for Trauma (FAST) is of questionable value. STUDY DESIGN: The trauma registry was queried over a 10-year period ending December 2013 for found down patients. Demographics, CT AP, FAST scans, and injuries were abstracted from the trauma registry and then through a confirmatory chart review. The primary outcome was significant abdominal or pelvis injury, defined as abdomen/pelvis Abbreviated Injury Scale (AIS) ≥ 3 or an abdominal injury that required operative intervention. The secondary outcome was mortality due to abdominal injury. RESULTS: Of the 342 patients who met inclusion criteria, mean Glasgow Coma Scale (GCS) was 11.0, and 189 (60%) of those tested for alcohol were intoxicated. Abdominal imaging included: CT AP only, 88 (57%); FAST only, 37 (24%); and CT AP and FAST, 29 (19%). Neither CT AP nor FAST scan led to a change in treatment and no patient had abdomen/pelvis AIS ≥ 3. Overall mortality was 33 (10%).The 24 trauma deaths were attributed to serious head trauma (n = 16) or traumatic arrest in the ED (n = 8); the 9 medical deaths were due to cerebral vascular accident (n = 5) or sepsis (n = 4). CONCLUSIONS: Although patients found down have a high mortality, abdominal injuries identified by imaging are highly unlikely. Efforts should focus on rapidly identifying and treating other causes of mortality, especially trauma to the head and neck, or medical diagnoses such as cerebral vascular accident or sepsis.

Histologic subtypes of hepatoblastoma are characterized by differential canonical Wnt and Notch pathway activation in DLK+ precursors.

Hepatoblastoma is characterized by a diversity of differentiation patterns, some resembling stages of liver development, and occasionally associated with clinical behavior. Our hypothesis is that histologic microheterogeneity in hepatoblastoma correlates with molecular heterogeneity and reflects different stages of developmental arrest. We studied the activation status of the Wnt and Notch pathways and the differential expression of hepatocyte nuclear factor 4alpha, EGFR, and IGF2 genes, relevant to liver development and malignant transformation in histologic variants of hepatoblastoma. Eighty-seven percent of 32 hepatoblastoma cases studied carried CTNNB1 mutations within the ubiquitination domain. Large deletions were seen only in pure fetal cases, also characterized by CCND1 and GLUL (GS) overexpression. Hepatoblastomas with small-cell type appeared clearly distinct and were the only ones with negative GLUL expression. HES1 expression and HES1/AXIN2 used to measure Notch versus Wnt activation ratio were particularly elevated in pure fetal cases and were lowest in hepatoblastomas with small-cell component. Hepatocyte nuclear factor 4alpha was relatively elevated only in embryonal hepatoblastomas. DLK1, DKK, AXIN2, IGF2, and EGFR were increased in all subtypes. Our results support the hypothesis that hepatoblastoma microheterogeneity correlates with molecular heterogeneity. DLK1, a marker of bipotential oval cells, is consistently up-regulated in hepatoblastoma. Therefore, we speculate that hepatoblastomas may arise from a proliferating bipotential precursor. Wnt activation is prevalent in hepatoblastomas, most significantly in predominantly embryonal and mixed types, whereas Notch activation, needed for cholangiocytic differentiation at a more differentiated state, is highest in pure fetal hepatoblastomas. The relative Wnt versus Notch activation appears useful in stratifying different subtypes.

Novel microRNA candidates and miRNA-mRNA pairs in embryonic stem (ES) cells.

BACKGROUND: MicroRNAS (miRNAS: a class of short non-coding RNAs) are emerging as important agents of post transcriptional gene regulation and integral components of gene networks. MiRNAs have been strongly linked to stem cells, which have a remarkable dual role in development. They can either continuously replenish themselves (self-renewal), or differentiate into cells that execute a limited number of specific actions (pluripotence). METHODOLOGY/PRINCIPAL FINDINGS: In order to identify novel miRNAs from narrow windows of development we carried out an in silico search for micro-conserved elements (MCE) in adult tissue progenitor transcript sequences. A plethora of previously unknown miRNA candidates were revealed including 545 small RNAs that are enriched in embryonic stem (ES) cells over adult cells. Approximately 20% of these novel candidates are down-regulated in ES (Dicer(-/-)) ES cells that are impaired in miRNA maturation. The ES-enriched miRNA candidates exhibit distinct and opposite expression trends from mmu-mirs (an abundant class in adult tissues) during retinoic acid (RA)-induced ES cell differentiation. Significant perturbation of trends is found in both miRNAs and novel candidates in ES (GCNF(-/-)) cells, which display loss of repression of pluripotence genes upon differentiation. CONCLUSION/SIGNIFICANCE: Combining expression profile information with miRNA target prediction, we identified miRNA-mRNA pairs that correlate with ES cell pluripotence and differentiation. Perturbation of these pairs in the ES (GCNF(-/-)) mutant suggests a role for miRNAs in the core regulatory networks underlying ES cell self-renewal, pluripotence and differentiation.