Blood volume measured by ultrasound and radioisotope dilution in critically ill subjects.

BACKGROUND: Accurate bedside assessment of circulating blood volume (BV) continues to challenge clinicians in their attempt to implement goal-directed therapy in the critically ill subject. The aim of this investigation was to comparatively evaluate BV measurements obtained by ultrasound and radioisotope dilution methodologies in adult subjects admitted to a surgical intensive care unit. MATERIALS AND METHODS: Fifty subjects with concurrent central venous catheters and peripheral arterial lines underwent measurement of BV using both ultrasound and radioisotope dilution (BV-RD) methods. The ultrasound dilution method was performed using a 30-mL injectate (BV-UD30) and a 60-mL injectate (BV-UD60) of isotonic saline. RESULTS: There were 24 paired data points for the BV-UD30 and 40 paired data points for the BV-UD60 measurements. Spearman's rank-order correlation demonstrated a positive relationship comparing both the BV-UD30 (r = 0.46, P = 0.0249) and the BV-UD60 (r = 0.80, P < 0.0001) to values obtained by radioisotope measurements. Bland-Altman analysis showed a mean bias of 1329 mL with limits of agreement (LOA) ± 2559 mL comparing BV-RD and BV-UD30, and a mean bias of 62 mL with LOA ±1353 mL for BV-RD and BV-UD60. CONCLUSIONS: This preliminary investigation shows that the BV-UD60 had better agreement with BV-RD, compared with the BV-UD30, but its utility appears limited by a large LOA. As this technology continues to evolve, the ultrasound dilution approach may potentially become a feasible means to calculate BV in critically ill surgical subjects.

Gene expression in fetal murine keratinocytes and fibroblasts.

BACKGROUND: Early fetuses heal wounds without the formation of a scar. Many studies have attempted to explain this remarkable phenomenon. However, the exact mechanism remains unknown. Herein, we examine the predominant cell types of the epidermis and dermis--the keratinocyte and fibroblast--during different stages of fetal development to better understand the changes that lead to scarring wound repair versus regeneration. MATERIALS AND METHODS: Keratinocytes and fibroblasts were harvested and cultured from the dorsal skin of time-dated BALB/c fetuses. Total RNA was isolated and microarray analysis was performed using chips with 42,000 genes. Significance analysis of microarrays was used to select genes with >2-fold expression differences with a false discovery rate<2. Enrichment analysis was performed on significant genes to identify differentially expressed pathways. RESULTS: By comparing the gene expression profile of keratinocytes from E16 versus E18 fetuses, we identified 24 genes that were downregulated at E16. Analysis of E16 and E18 fibroblasts revealed 522 differentially expressed genes. Enrichment analysis showed the top 20 signaling pathways that were downregulated in E16 keratinocytes and upregulated or downregulated in E16 fibroblasts. CONCLUSIONS: Our data reveal 546 differentially expressed genes in keratinocytes and fibroblasts between the scarless and scarring transition. In addition, a total of 60 signaling pathways have been identified to be either upregulated or downregulated in these cell types. The genes and pathways recognized by our study may prove to be essential targets that may discriminate between fetal wound regeneration and adult wound repair.

Brain-type natriuretic peptide and right ventricular end-diastolic volume index measurements are imprecise estimates of circulating blood volume in critically ill subjects.

BACKGROUND: Surrogate indicators have often been used to estimate intravascular volume to guide fluid management. Brain-type natriuretic peptide (BNP) has been used as a noninvasive adjunct in the diagnosis of fluid overload and as a marker of response to therapy, especially in individuals with congestive heart failure. Similarly, right ventricular end-diastolic volume index (RVEDVI) measurements represent another parameter used to guide fluid resuscitation. The aim of this study was to evaluate whether BNP and RVEDVI are clinically valuable parameters that can distinguish among hypovolemia, euvolemia, and hypervolemia, as measured by blood volume (BV) analysis in critically ill surgical subjects. METHODS: This observational study was part of a prospective, randomized controlled trial. Subjects with pulmonary artery catheters for the treatment of traumatic injuries, severe sepsis/septic shock, cardiovascular collapse, adult respiratory distress syndrome, and postsurgical care were studied. Circulating BV was measured by a radioisotope dilution technique using the BVA-100 Analyzer (Daxor Corporation, New York, NY) within the first 24 hours of acute resuscitation. BV results were reported as percent deviation from the patient's ideal BV based on height and percent deviation from optimum weight. Hypovolemia was defined as less than 0%, euvolemia was defined as 0% to +16%, and hypervolemia was defined as greater than +16% deviation from ideal BV. RVEDVI was measured by continuous cardiac output pulmonary artery catheters (Edwards Lifesciences, Irvine, CA). BNP and RVEDVI measurements obtained with BV analysis were evaluated with Fisher's exact test and regression analysis. RESULTS: In 81 subjects, there was no difference in BV status between those with BNP of 500 pg/mL or greater and BNP of less than 500 pg/mL (p = 0.82) or in those with RVEDVI of 140 mL/m or greater and RVEDVI of less than 140 mL/m (p = 0.43). No linear relationship existed between BV and these parameters. CONCLUSION: In critically ill surgical patients, BNP and RVEDVI were not associated with intravascular volume status, although they may be useful as indices that reflect increased cardiac preload. LEVEL OF EVIDENCE: Diagnostic study, level III.

Effect of the 16-hour work limit on general surgery intern operative case volume: a multi-institutional study.

IMPORTANCE: The 80-hour work-week limit for all residents was instituted in 2003 and studies looking at its effect have been mixed. Since the advent of the 16-hour mandate for postgraduate year 1 residents in July 2011, no data have been published regarding the effect of this additional work-hour restriction. OBJECTIVE: To determine whether the 16-hour intern work limit, implemented in July 2011, has adversely affected operative experience. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of categorical postgraduate year 1 Accreditation Council for Graduate Medical Education case logs from the intern class (N = 52) (with 16-hour work limit) compared with the 4 preceding years (2007-2010; N = 197) (without 16-hour work limit). A total of 249 categorical general surgery interns from 10 general surgery residency programs in the western United States were included. MAIN OUTCOMES AND MEASURES: Total, major, first-assistant, and defined-category case totals. RESULTS: As compared with the preceding 4 years, the 2011-2012 interns recorded a 25.8% decrease in total operative cases (65.9 vs 88.8, P = .005), a 31.8% decrease in major cases (54.9 vs 80.5, P < .001), and a 46.3% decrease in first-assistant cases (11.1 vs 20.7, P = .008). There were statistically significant decreases in cases within the defined categories of abdomen, endocrine, head and neck, basic laparoscopy, complex laparoscopy, pediatrics, thoracic, and soft tissue/breast surgery in the 16-hour shift intern era, whereas there was no decrease in trauma, vascular, alimentary, endoscopy, liver, and pancreas cases. CONCLUSIONS AND RELEVANCE: The 16-hour work limit for interns, implemented in July 2011, is associated with a significant decrease in categorical intern operative experience. If the 16-hour shift were to be extended to all postgraduate year levels, one can anticipate that additional years of training will be needed to maintain the same operative volume.

Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive Retroperitoneal Hemorrhage.

Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers-Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1 chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A number of previous reports describe futile surgical intervention for retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post-operative mortality, although the rarity of retroperitoneal bleeding associated with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to clinical management. We report a 23-year-old male with history of Type-IV Ehlers-Danlos Syndrome who presented with severe abdominal pain and tachycardia following an episode of vomiting. Further work-up of his abdominal pain revealed massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos Syndrome, the patient was treated non-operatively, and the patient made a full recovery. This case suggests that even in cases of large retroperitoneal hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a surgical emergency.

Preventing loss of domain: a management strategy for closure of the "open abdomen" during the initial hospitalization.

BACKGROUND: In the management of the abdominal compartment syndrome resulting in an open abdomen, the so-called "planned ventral hernia" is considered an acceptable outcome. We describe a technique of surgical management of the abdominal wound that allows fascial closure in most cases during the initial admission. METHODS: Consecutive trauma patients with abdominal compartment syndrome managed with an open abdomen over a 3-year period were identified. Medical records and the trauma data registry were reviewed for demographics, injury characteristics, operative treatment, timing and type of wound management, closure of the abdomen, and outcome. RESULTS: From January 2004 to January 2007, 23 patients underwent management with an open abdomen. The mechanism of injury was blunt in 83% of patients and penetrating in 17%. All 18 survivors underwent primary fascial closure of the abdomen using a vacuum- and tie-assisted technique of wound closure. The mean time to closure was 11 +/- 4.4 days (range, 4-18 days). In all, 9 complications occurred in 7 patients, which included 1 reoperation for abscess after fascial closure. There was no dehiscence and no fistula. The Apache II score was 19.3 +/- 6.9 (range, 7-30), and the injury severity score was 32.3 + 10.6 (range, 9-50). CONCLUSIONS: A technique of managing the open abdomen that prevents fascial retraction results in a high primary closure rate with an acceptable rate of short-term complications.

The need for a standardized evaluation method to assess efficacy of cultural competence initiatives in medical education and residency programs.

Cultural competence education is relatively new in the United States, particularly in the area of graduate and post-graduate medical education. There is, however, wide acceptance that an understanding of the role culture plays in the treatment and care of patients is critical. Numerous studies and a variety of commentaries document this importance, but valid, uniform evaluation methods for assessing the efficacy of these efforts is lacking. This review discusses existing evaluation efforts and makes suggestions regarding future development of such tools.

The availability of circulating blood volume values alters fluid management in critically ill surgical patients.

BACKGROUND: This study evaluated whether commercially available blood volume measurements in critically ill surgical patients altered fluid management. METHODS: Patients admitted to the surgical intensive care unit of a tertiary care teaching hospital were prospectively evaluated. The frequency of changes in fluid management when results of blood volume measurements were available was determined. RESULTS: In a pilot study, the frequency of instances when measurement of blood volume would have altered fluid management was statistically significant (P = .0003). In 40 subsequent patients, treatment change occurred in 36% of instances when blood volume results were obtained (P < .001). In the majority, no immediate qualitative change in clinical status occurred, with a desirable clinical response in 39% and no negative treatment responses (P < .001). CONCLUSIONS: Blood volume measurements may assist in the management of critically ill surgical patients by providing a direct measure of intravascular volume. Further studies are warranted to determine its effect on outcome.

Twenty-eight-day mortality in critically ill surgical patients is an imprecise temporal end-point measure for in-hospital mortality.

BACKGROUND: The purpose of this study was to determine the incidence of deaths occurring beyond 28 days in critically ill surgical patients and to identify the proportion of these deaths attributable to the original disease process. METHODS: Analysis of 1,360 subjects admitted to a surgical intensive care unit during a 2 year period. Demographics, indication(s) for admission, comorbidities, mortality rate, multiorgan failure development, and cause of death was obtained. RESULTS: Mortality rate in the surgical intensive care unit was 12%. Twenty % of deaths occurred more than 28 days after hospital admission with 76% of deaths related to admission diagnosis. By day 34, 95% of mortalities had occurred. CONCLUSIONS: The 28-day time period used to assess efficacy of therapeutic interventions and to define mortality in the context of quality audits should be questioned. If these findings are validated in other centers another temporal end point for in-hospital mortality should be considered.

Using transcutaneous oxygen pressure measurements as selection criteria for activated protein C use.

BACKGROUND: Limited resources and the expense of Activated Protein C (APC) (drotrecogin alfa) may contribute to the reluctance to utilize this drug in sepsis. Employing the PROWESS criteria resulted in absolute reduction in 28-day mortality of 6.1%, representing a relative risk reduction of 19.4%. Additional patient categorization and selection may lead to less frequent drug use with the same survival advantage. We used transcutaneous partial pressure of oxygen (PtcO2) as an indicator of microcirculatory perfusion to identify which septic patients may benefit from APC. METHODS: Nineteen patients consecutively admitted with severe sepsis or septic shock that fulfilled the PROWESS criteria for APC treatment. APC was administered to patients with the PROWESS selection criteria, only if the PtcO2 information demonstrated tissue ischemia. RESULTS: Nineteen patients met the PROWESS criteria. Ten patients demonstrated poor tissue perfusion using PtcO2 monitors and received APC. Nine patients had adequate tissue perfusion and did not receive APC. There were no differences in age, gender, APACHE II scores, lactate levels, or organ failure between the two groups. The 10 patients who received APC had a mortality of 3 of 10 (30%). The survivors of this group uniformly converted to PtcO2 values consistent with survival within 12 hours to 24 hours of drug administration. The nine patients who did not receive APC had a mortality of 2 of 9 (22%), not statistically significant from those who received the drug (p = 0.89). CONCLUSION: Withholding APC did not result in an increase in mortality from severe sepsis in those patients who demonstrated adequate PtcO2 values. The transcutaneous oxygen measurement may be a useful adjuvant in addition to the other selection criteria for better identification of patients who may benefit from APC.

Peripheral blood hematocrit in critically ill surgical patients: an imprecise surrogate of true red blood cell volume.

BACKGROUND: Peripheral blood hematocrit (red blood cell volume/total blood volume) is conventionally used to determine the need for blood transfusions. In critically ill surgical patients, this variable may not accurately approximate true red blood cell volume. We compared peripheral blood hematocrit to (1) plasma volume, (2) estimated circulating blood volume, and (3) a normalized hematocrit to clarify their relationships. METHODS: Consecutive patients admitted to the surgical intensive care unit were evaluated using the BVA-100 Blood Volume Analyzer (Daxor Corporation, New York City, NY). Plasma volume was directly measured by serial tagged albumin concentration. Red blood cell volume was calculated using plasma volume and the peripheral blood hematocrit result. All volumes were presented as percentage deviation from ideal volumes. These ideal volumes were obtained using a patented formula incorporating ideal body weight as determined by Metropolitan Life tables. The peripheral blood hematocrit was compared with a "normalized" hematocrit, defined as the hematocrit value if plasma volume was adjusted to a normal whole blood volume. RESULTS: Eighty-six data points were recorded for 40 patients with average age 61 +/- 20 yr, APACHE II score 20 +/- 6, and a 13% mortality rate. The primary reasons for admission were severe sepsis/septic shock (n = 11), hemorrhagic shock (n = 7), respiratory failure (n = 20), and cardiac failure (n = 2). Bland-Altman analysis showed a mean difference of 3.4 +/- 7.8 hematocrit percentage points between normalized and peripheral blood hematocrit methods, with a 95% confidence interval of 1.7-5.1 and limits of agreement of +/-15.2 hematocrit percentage points. Peripheral blood hematocrit was lower than the normalized hematocrit in 48% of measurements, higher in 17%, and equivalent in 35%. CONCLUSIONS: Peripheral blood hematocrit may not accurately estimate red blood cell volume in a cohort of critically ill surgical patients. This remains to be validated in a larger group of patients, comparing these results with the double isotope technique.

Circulating blood volume measurements correlate poorly with pulmonary artery catheter measurements.

BACKGROUND: Determination of the intravascular volume status of a critically ill surgical patient is paramount for appropriate fluid and cardiovascular management. Many clinical parameters have been utilized to estimate intravascular volume but none are precise indicators of circulating blood volume. The purpose of this observational pilot study was to compare measured blood volume with hemodynamic parameters obtained from the pulmonary artery catheter and to determine if incorporation of these measurements altered treatment decisions in critically ill surgical patients. METHODS: Blood volume measurements were prospectively obtained in twenty surgical intensive care unit patients with a pulmonary artery catheter when intravascular volume status was deemed uncertain by traditional clinical parameters. RESULTS: There was a statistically significant, but weak, correlation between blood volume results and pulmonary artery occlusion pressure, but no correlation with central venous pressure, cardiac index, and stroke volume index. Blood volume information altered treatment in 21% of instances, and 5 of these 6 patients demonstrated a favorable clinical response. CONCLUSIONS: Circulating blood volume measurements may be useful in critically ill surgical patients when clinical appraisal of intravascular volume is uncertain. This remains to be validated in a larger, prospective randomized trial.

Determination of reference ranges for transcutaneous oxygen and carbon dioxide tension and the oxygen challenge test in healthy and morbidly obese subjects.

BACKGROUND: Transcutaneous monitoring of oxygen and carbon dioxide tension emerged decades ago as reliable, indirect measurements of arterial pressure of oxygen and carbon dioxide in neonates. Investigators have since found other valuable roles for this modality, particularly in critically ill adults. This investigation was undertaken to further characterize these measurements in normal and in obese adults, who are contributing to a rising proportion of intensive care unit admissions. MATERIALS AND METHODS: Transcutaneous sensors were adjusted for barometric pressure and calibrated to reference gases. The following were measured: equilibration time; oxygen saturation; transcutaneous oxygen tension; and transcutaneous carbon dioxide tension on room air and after administering fraction of inspired oxygen of 1.0 for 5 min (Oxygen Challenge Test). RESULTS: One hundred three healthy and 47 obese subjects were enrolled. Oxygen Challenge Test values were 131.5 +/- 57.4 and 171.6 +/- 65.9 mm Hg for obese and healthy subjects, respectively (P value <0.001). Smoking status, respiratory rate, and transcutaneous oxygen tension on room air best predicted the Oxygen Challenge Test response. A negative correlation was found between transcutaneous oxygen on room air and the Oxygen Challenge Test versus body mass index (P < 0.001). CONCLUSIONS: Reference ranges were determined for transcutaneous oxygen and carbon dioxide tension and the Oxygen Challenge Test in obese and in normal, healthy subjects. Increasing body mass index was associated with a lower baseline transcutaneous oxygen tension, but it was not an independent predictor of the Oxygen Challenge Test response in multivariate analysis.

Increased fatalities and cost of traumatic injuries in elderly pedestrians in Hawaii: a challenge for prevention and outreach.

This study was carried out to evaluate and quantify risk factors, mechanisms, and cost of traumatic injuries in Hawaii's elderly and to identify potential preventive strategies. A retrospective review of a prospective database of patients admitted to the only Trauma Center in the Pacific Basin, between January 2000 and December 2001, was conducted. Of 2634 trauma admissions, 11% were >or=65 years of age. Mechanisms of injury included falls, motor vehicle crashes (MVCs), pedestrians hit by automobiles, and miscellaneous causes. The incidence of elderly pedestrians hit by automobiles in Hawaii is higher than previously reported. Hospital mortality rate was highest for the pedestrian hit group, followed by falls, and then MVCs. The pedestrian hit group consumed the largest quantity of resources and MVCs the least. Given the high mortality rate and associated resource consumption in the pedestrian hit group, it would be appropriate to give priority to this group while developing preventive measures for this age group.

Other primary neoplasms in patients with hepatocellular cancer: prognostic implications?

PURPOSE: Little is known about other primary neoplasms occurring in patients with hepatocellular cancer (HCC). This team attempted to characterize this cohort of patients to define incidence, risk factors, natural history, and potentially shared etiologies. METHODS: A retrospective analysis from an established, prospective database of patients with HCC during 1991-2004 was used to determine demographic data, risk factors, characteristics of the associated second primary neoplasm, and survival. MAIN FINDINGS: Of 306 patients with HCC, 23 patients (7.5%) were identified with a second neoplasm. Two of these patients had a third neoplasm. Mean age was 65.6 years and male:female ratio was 2.3:1. Risk factors included: hepatitis B (27.3%), hepatitis C (40.9%), smoking (17.4 %), diabetes (26.1%), cirrhosis (63.6%), and family history of HCC (4.5%). Second associated primaries included 7 genitourinary (prostate--2, bladder--2, testicular--1, renal--1, ovarian--1), 7 gastrointestinal (colon--6, gastric--1), 3 breast, 2 skin, 2 lung, 2 hematologic, 1 tongue, and 1 desmoid. Four patients had HCC first, 1 patient had synchronous HCC and colon cancer, while 18 had the other primary first. Mean, 1 and 2-year survival after diagnosis of HCC was 1014.8 days, 75%, and 30%, compared to 782.6 days, 54.6%, and 41.1%, respectively, in the group with HCC only (p > 0.05). CONCLUSION: The incidence of other primary tumors in the setting of HCC is relatively common with a strong clustering of genitourinary and gastrointestinal malignancies. There was no statistically significant difference in overall survival compared to patients with HCC only, suggesting that the association of other primary tumors with HCC does not confer a worse prognosis.