The Upper Limit of Cerebral Blood Flow Autoregulation Is Decreased with Elevations in Intracranial Pressure.

BACKGROUND: The upper limit of cerebrovascular pressure autoregulation (ULA) is inadequately characterized. We sought to delineate the ULA in a neonatal swine model. METHODS: Neonatal piglets with sham surgery (n = 9), interventricular fluid infusion (INF; n = 10), controlled cortical impact (CCI; n = 10), or impact + infusion (CCI + INF; n = 11) had intracranial pressure monitoring and bilateral cortical laser-Doppler flux recordings during arterial hypertension until lethality. An increase in red cell flux as a function of cerebral perfusion pressure was determined by piecewise linear regression and static rates of autoregulation (SRoRs) were determined above and below this inflection. RESULTS: When identified, the ULA (median [interquartile range]) was as follows: sham group: 102 mmHg (97-109), INF group: 75 mmHg (52-84), CCI group: 81 mmHg (69-101), and CCI + INF group: 61 mmHg (52-57; p = 0.01). Both groups with interventricular infusion had significantly lower ULA compared with the sham group. CONCLUSION: Neonatal piglets without intracranial pathological conditions tolerated acute hypertension, with minimal perturbation of cerebral blood flow. Piglets with acutely elevated intracranial pressure, with or without trauma, demonstrated loss of autoregulation when subjected to arterial hypertension.

Noncardiac Challenges in the Cardiac ICU: Feeding, Growth and Gastrointestinal Complications, Anticoagulation, and Analgesia.

Outcomes following cardiac intensive care unit (CICU) admission are influenced by many factors including initial cardiac diagnosis, surgical complexity, and burden of critical illness. Additionally, the presence of noncardiac issues may have a significant impact on outcomes and the patient experience during and following an intensive care unit stay. This review focuses on three common noncardiac areas which impact outcomes and patient experience in and beyond the CICU: feeding and growth, pain and analgesia, and anticoagulation. Growth failure and feeding dysfunction are commonly encountered in infants requiring cardiac surgery and have been associated with worse surgical and developmental outcomes. Recent studies most notably in the single ventricle population have demonstrated improved weight gain and outcomes when feeding protocols are implemented. Children undergoing cardiac surgery may experience both acute and chronic pain. Emerging research is investigating the impact of sedatives and analgesics on neurodevelopmental outcomes and quality of life. Improved pain scores and standardized management of pain and withdrawal may improve the patient experience and outcomes. Effective anticoagulation is a critical component of perioperative care but may be complicated by inflammation, multiorgan dysfunction, and patient factors. Advances in monitoring of anticoagulation and emerging therapies are reviewed.

The upper limit of cerebral blood flow autoregulation is decreased with elevations in intracranial pressure.

BACKGROUND: The upper limit of cerebrovascular pressure autoregulation (ULA) is inadequately characterized. OBJECTIVE: To delineate the ULA in an infant swine model. METHODS: Neonatal piglets with sham surgery (n = 9), interventricular fluid infusion (INF) (n = 10), controlled cortical impact (CCI) (n = 10), or CCI + INF (n = 11) had intracranial pressure monitoring and bilateral cortical laser-Doppler flowmetry recordings during arterial hypertension to lethality using an aortic balloon catheter. An increase of red cell flux as a function of cerebral perfusion pressure was determined by piecewise linear regression, and static rates of autoregulation were determined above and below this inflection. The ULA was rendered as the first instance of an upward deflection of Doppler flux causing a static rate of autoregulation decrease greater than 0.5. RESULTS: ULA was identified in 55% of piglets after sham surgery, 70% after INF, 70% after CCI, and 91% after CCI with INF (P = .36). When identified, the median (interquartile range) ULA was as follows: sham group, 102 mm Hg (97-109 mm Hg); INF group, 75 mm Hg (52-84 mm Hg); CCI group, 81 mm Hg (69-101 mm Hg); and CCI + INF group, 61 mm Hg (52-57 mm Hg) (P = .01). In post hoc analysis, both groups with interventricular INF had significantly lower ULA than that observed in the sham group. CONCLUSION: Neonatal piglets without intracranial pathology tolerated acute hypertension with minimal perturbation of cerebral blood flow. Piglets with acutely increased intracranial pressure with or without trauma demonstrated loss of autoregulation when subjected to arterial hypertension.

Duration and magnitude of blood pressure below cerebral autoregulation threshold during cardiopulmonary bypass is associated with major morbidity and operative mortality.

OBJECTIVES: Optimizing blood pressure using near-infrared spectroscopy monitoring has been suggested to ensure organ perfusion during cardiac surgery. Near-infrared spectroscopy is a reliable surrogate for cerebral blood flow in clinical cerebral autoregulation monitoring and might provide an earlier warning of malperfusion than indicators of cerebral ischemia. We hypothesized that blood pressure below the limits of cerebral autoregulation during cardiopulmonary bypass would be associated with major morbidity and operative mortality after cardiac surgery. METHODS: Autoregulation was monitored during cardiopulmonary bypass in 450 patients undergoing coronary artery bypass grafting and/or valve surgery. A continuous, moving Pearson's correlation coefficient was calculated between the arterial pressure and low-frequency near-infrared spectroscopy signals and displayed continuously during surgery using a laptop computer. The area under the curve of the product of the duration and magnitude of blood pressure below the limits of autoregulation was compared between patients with and without major morbidity (eg, stroke, renal failure, mechanical lung ventilation >48 hours, inotrope use >24 hours, or intra-aortic balloon pump insertion) or operative mortality. RESULTS: Of the 450 patients, 83 experienced major morbidity or operative mortality. The area under the curve of the product of the duration and magnitude of blood pressure below the limits of autoregulation was independently associated with major morbidity or operative mortality after cardiac surgery (odds ratio, 1.36; 95% confidence interval, 1.08-1.71; P = .008). CONCLUSIONS: Blood pressure management during cardiopulmonary bypass using physiologic endpoints such as cerebral autoregulation monitoring might provide a method of optimizing organ perfusion and improving patient outcomes from cardiac surgery.

Computerized physician order entry improves compliance with a manual exchange transfusion protocol in the pediatric intensive care unit.

AIM: To evaluate the use of a computerized physician order entry (CPOE) protocol on manual red blood cell (RBC) exchange transfusion in critically ill children with sickle cell disease. METHODS: We conducted a retrospective study of children with sickle cell disease who received a manual RBC exchange transfusion before (2001 to 2008, n=22) and after (2008 to 2009, n=11) implementation of a CPOE protocol. Outcomes included compliance with protocol, percentage reduction in sickle hemoglobin, and peak hemoglobin during exchange. RESULTS: Compliance with the manual exchange protocol improved after introduction of CPOE (pre-CPOE: 20 protocol violations vs. post-CPOE: 3 violations, P=0.02). Percentage reduction in sickle hemoglobin also improved (pre-CPOE: 55% vs. post-CPOE: 70%, P=0.04), whereas peak hemoglobin during RBC exchange was similar (pre-CPOE: 12.0 g/dL vs. post-CPOE: 11.5 g/dL, P=0.25). However, hemoglobin levels after the mean of 7 hours of exchange were significantly higher pre-CPOE (pre-CPOE: 11.5 g/dL vs. post-CPOE: 10.5 g/dL, P=0.006). CONCLUSIONS: Use of CPOE for manual RBC exchange transfusion in children is associated with improved protocol compliance, improved reduction of sickle hemoglobin, and better maintenance of hemoglobin levels in a goal range during prolonged exchanges.

Glial fibrillary acidic protein in children with congenital heart disease undergoing cardiopulmonary bypass.

OBJECTIVE: To determine whether blood levels of the brain-specific biomarker glial fibrillary acidic protein rise during cardiopulmonary bypass for repair of congenital heart disease. METHODS: This is a prospective observational pilot study to characterise the blood levels of glial fibrillary acidic protein during bypass. Children <21 years of age undergoing bypass for congenital heart disease at Johns Hopkins Hospital and Texas Children's Hospital were enrolled. Blood samples were collected during four phases: pre-bypass, cooling, re-warming, and post-bypass. RESULTS: A total of 85 patients were enrolled between October, 2010 and May, 2011. The median age was 0.73 years (range 0.01-17). The median weight was 7.14 kilograms (range 2.2-86.5). Single ventricle anatomy was present in 18 patients (22%). Median glial fibrillary acidic protein values by phase were: pre-bypass: 0 ng/ml (range 0-0.35); cooling: 0.039 (0-0.68); re-warming: 0.165 (0-2.29); and post-bypass: 0.112 (0-0.97). There were significant elevations from pre-bypass to all subsequent stages, with the greatest increase during re-warming (p = 0.0001). Maximal levels were significantly related to younger age (p = 0.03), bypass time (p = 0.03), cross-clamp time (p = 0.047), and temperature nadir (0.04). Peak levels did not vary significantly in those with single ventricle anatomy versus two ventricle repairs. CONCLUSION: There are significant increases in glial fibrillary acidic protein levels in children undergoing cardiopulmonary bypass for repair of congenital heart disease. The highest values were seen during the re-warming phase. Elevations are significantly associated with younger age, bypass and cross-clamp times, and temperature nadir. Owing to the fact that glial fibrillary acidic protein is the most brain-specific biomarker identified to date, it may act as a rapid diagnostic marker of brain injury during cardiac surgery.

Neurodevelopmental outcomes after regional cerebral perfusion with neuromonitoring for neonatal aortic arch reconstruction.

BACKGROUND: In this study we report magnetic resonance imaging (MRI) brain injury and 12-month neurodevelopmental outcomes when regional cerebral perfusion (RCP) is used for neonatal aortic arch reconstruction. METHODS: Fifty-seven neonates receiving RCP during aortic arch reconstruction were enrolled in a prospective outcome study. RCP flows were determined by near-infrared spectroscopy and transcranial Doppler monitoring. Brain MRI was performed preoperatively and 7 days postoperatively. Bayley Scales of Infant Development III was performed at 12 months. RESULTS: Mean RCP time was 71 ± 28 minutes (range, 5 to 121 minutes) and mean flow was 56.6 ± 10.6 mL/kg/min. New postoperative MRI brain injury was seen in 40% of patients. For 35 RCP patients at age 12 months, mean Bayley Scales III Composite standard scores were: Cognitive, 100.1 ± 14.6 (range, 75 to 125); Language, 87.2 ± 15.0 (range, 62 to 132); and Motor, 87.9 ± 16.8 (range, 58 to 121). Increasing duration of RCP was not associated with adverse neurodevelopmental outcomes. CONCLUSIONS: Neonatal aortic arch repair with RCP using a neuromonitoring strategy results in 12-month cognitive outcomes that are at reference population norms. Language and motor outcomes are lower than the reference population norms by 0.8 to 0.9 standard deviations. The neurodevelopmental outcomes in this RCP cohort demonstrate that this technique is effective and safe in supporting the brain during neonatal aortic arch reconstruction.

Blood pressure excursions below the cerebral autoregulation threshold during cardiac surgery are associated with acute kidney injury.

OBJECTIVES: To determine whether mean arterial blood pressure excursions below the lower limit of cerebral blood flow autoregulation during cardiopulmonary bypass are associated with acute kidney injury after surgery. SETTING: Tertiary care medical center. PATIENTS: Four hundred ten patients undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective observational study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Autoregulation was monitored during cardiopulmonary bypass by calculating a continuous, moving Pearson's correlation coefficient between mean arterial blood pressure and processed near-infrared spectroscopy signals to generate the variable cerebral oximetry index. When mean arterial blood pressure is below the lower limit of autoregulation, cerebral oximetry index approaches 1, because cerebral blood flow is pressure passive. An identifiable lower limit of autoregulation was ascertained in 348 patients. Based on the RIFLE criteria (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease), acute kidney injury developed within 7 days of surgery in 121 (34.8%) of these patients. Although the average mean arterial blood pressure during cardiopulmonary bypass did not differ, the mean arterial blood pressure at the limit of autoregulation and the duration and degree to which mean arterial blood pressure was below the autoregulation threshold (mm Hg × min/hr of cardiopulmonary bypass) were both higher in patients with acute kidney injury than in those without acute kidney injury. Excursions of mean arterial blood pressure below the lower limit of autoregulation (relative risk 1.02; 95% confidence interval 1.01 to 1.03; p < 0.0001) and diabetes (relative risk 1.78; 95% confidence interval 1.27 to 2.50; p = 0.001) were independently associated with for acute kidney injury. CONCLUSIONS: Excursions of mean arterial blood pressure below the limit of autoregulation and not absolute mean arterial blood pressure are independently associated with for acute kidney injury. Monitoring cerebral oximetry index may provide a novel method for precisely guiding mean arterial blood pressure targets during cardiopulmonary bypass.

Cerebral blood flow autoregulation is preserved after continuous-flow left ventricular assist device implantation.

OBJECTIVE: To compare cerebral blood flow (CBF) autoregulation in patients undergoing continuous-flow left ventricular assist device (LVAD) implantation with that in patients undergoing coronary artery bypass grafting (CABG). DESIGN: Prospective, observational, controlled study. SETTING: Academic medical center. PARTICIPANTS: Fifteen patients undergoing LVAD insertion and 10 patients undergoing CABG. MEASUREMENTS AND MAIN RESULTS: Cerebral autoregulation was monitored with transcranial Doppler and near-infrared spectroscopy. A continuous Pearson correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity and between MAP and near-infrared spectroscopic data, rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Mx and COx approach 0 when autoregulation is intact (no correlation between CBF and MAP), but approach 1 when autoregulation is impaired. Mx was lower during and immediately after cardiopulmonary bypass in the LVAD group than in the CABG group, indicating better-preserved autoregulation. Based on COx monitoring, autoregulation tended to be better preserved in the LVAD group than in the CABG group immediately after surgery (p = 0.0906). On postoperative day 1, COx was lower in the LVAD group than in the CABG group, indicating preserved CBF autoregulation (p = 0.0410). Based on COx monitoring, 3 patients (30%) in the CABG group had abnormal autoregulation (COx ≥0.3) on the first postoperative day but no patient in the LVAD group had this abnormality (p = 0.037). CONCLUSIONS: These data suggest that CBF autoregulation is preserved during and immediately after surgery in patients undergoing LVAD insertion.

Changing expectations for neurological outcomes after the neonatal arterial switch operation.

BACKGROUND: Expectations for outcomes after the neonatal arterial switch operation (ASO) continue to change. This cohort study describes neurodevelopmental outcomes at age 12 months after neonatal ASO, and analyzes both modifiable and nonmodifiable factors for association with adverse outcomes. METHODS: Patients who underwent an ASO (n=30) were enrolled in a prospective outcome study, with comprehensive clinical data collection during the first 12 months of life. Brain magnetic resonance imaging was done preoperatively and 7 days postoperatively, and the Bayley Scales of Infant Development III was performed at age 12 months. RESULTS: Ten of 30 patients (33%) had preoperative magnetic resonance imaging injury; 13 of 30 patients (43%) had new postoperative magnetic resonance imaging injury. Twenty patients (67%) had Bayley Scales of Infant Development III: Cognitive Composite standard score mean was 104.8±15.0, Language Composite standard score median was 90.0 (25th to 75th percentile, 83 to 94), and Motor Composite standard score mean was 92.3±14.2. Best subsets multivariable analysis found associations between lower preoperative and intraoperative cerebral oxygen saturation, preoperative magnetic resonance imaging brain injury, total bypass time, and total midazolam dose and lower Bayley Scales of Infant Development III scores at age 12 months. CONCLUSIONS: At 12 months after ASO, neurodevelopmental outcome means were within normal population ranges. The new associations reported in this study between potentially modifiable perioperative factors and outcomes require investigations in larger patient cohorts. Beyond survival, which was 100% in this cohort, factors influencing quality of life including neurodevelopmental outcomes should be routinely investigated in studies of ASO patients.

Predicting the limits of cerebral autoregulation during cardiopulmonary bypass.

BACKGROUND: Mean arterial blood pressure (MAP) targets are empirically chosen during cardiopulmonary bypass (CPB). We have previously shown that near-infrared spectroscopy (NIRS) can be used clinically for monitoring cerebral blood flow autoregulation. The hypothesis of this study was that real-time autoregulation monitoring using NIRS-based methods is more accurate for delineating the MAP at the lower limit of autoregulation (LLA) during CPB than empiric determinations based on age, preoperative history, and preoperative blood pressure. METHODS: Two hundred thirty-two patients undergoing coronary artery bypass graft and/or valve surgery with CPB underwent transcranial Doppler monitoring of the middle cerebral arteries and NIRS monitoring. A continuous, moving Pearson correlation coefficient was calculated between MAP and cerebral blood flow velocity and between MAP and NIRS data to generate mean velocity index and cerebral oximeter index. When autoregulated, there is no correlation between cerebral blood flow and MAP (i.e., mean velocity and cerebral oximetry indices approach 0); when MAP is below the LLA, mean velocity and cerebral oximetry indices approach 1. The LLA was defined as the MAP at which mean velocity index increased with declining MAP to ≥ 0.4. Linear regression was performed to assess the relation between preoperative systolic blood pressure, MAP, MAP in 10% decrements from baseline, and average cerebral oximetry index with MAP at the LLA. RESULTS: The MAP at the LLA was 66 mm Hg (95% prediction interval, 43 to 90 mm Hg) for the 225 patients in which this limit was observed. There was no relationship between preoperative MAP and the LLA (P = 0.829) after adjusting for age, gender, prior stroke, diabetes, and hypertension, but a cerebral oximetry index value of >0.5 was associated with the LLA (P = 0.022). The LLA could be identified with cerebral oximetry index in 219 (94.4%) patients. The mean difference in the LLA for mean velocity index versus cerebral oximetry index was -0.2 ± 10.2 mm Hg (95% CI, -1.5 to 1.2 mm Hg). Preoperative systolic blood pressure was associated with a higher LLA (P = 0.046) but only for those with systolic blood pressure ≤ 160 mm Hg. CONCLUSIONS: There is a wide range of MAP at the LLA in patients during CPB, making estimation of this target difficult. Real-time monitoring of autoregulation with cerebral oximetry index may provide a more rational means for individualizing MAP during CPB.

Anesthetic and perioperative risk in the patient with Ataxia-Telangiectasia.

OBJECTIVES/AIM: To report our relatively large experience with perioperative care for patients with Ataxia-Telangiectasia (A-T) and to identify the nature and frequency of complications. BACKGROUND: Ataxia-Telangiectasia is a rare autosomal recessive genetic disorder resulting in progressive multisystem degeneration and characteristic findings including complex neurodegeneration, immunodeficiency, increased risk of malignancy, and lung disease. Anecdotal reports have suggested high perioperative morbidity in patients with A-T, but few data exist. METHODS/MATERIALS: The Ataxia-Telangiectasia Clinical Center database was cross-referenced with operative records between 1995 and 2009 to identify patients with perioperative A-T, and medical records were reviewed for preoperative history, management techniques, and complications. RESULTS: Twenty-one patients with A-T underwent 34 anesthetics during the study period. The median age was 12.5 years (range 6-33 years). Common comorbidities included neurologic (100%), pulmonary (68%), immunologic (50%), oncologic (47%), and gastroenterologic (35%) disorders. Supplemental oxygen was required on postanesthesia care unit discharge for 24% of patients with a maximal duration of 24 h. Although mild postoperative hypothermia was relatively common (44% of anesthetics), there were no major complications, no unplanned admissions, and no mortality in this series. CONCLUSIONS: Although limited by its retrospective nature, this is the first series describing perioperative risk for patients with A-T. Our results indicate that general anesthesia, airway manipulation, and perioperative mechanical ventilation may be tolerated with only minor postoperative anesthetic concerns. Perioperative providers should be aware of the complex multisystem medical concerns that may arise in these patients.

Critical evaluation of emergency stockpile ventilators in an in vitro model of pediatric lung injury.

OBJECTIVE: Modern health care systems may be inadequately prepared for mass casualty respiratory failure requiring mechanical ventilation. Current health policy has focused on the "stockpiling" of emergency ventilators, though little is known about the performance of these ventilators under conditions of respiratory failure in adults and children. In this study, we seek to compare emergency ventilator performance characteristics using a test lung simulating pediatric lung injury. DESIGN: Evaluation of ventilator performance using a test lung. SETTING: Laboratory. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six transport/emergency ventilators capable of adult/child application were chosen on the basis of manufacturer specifications, Autovent 3000, Eagle Univent 754, EPV 100, LP-10, LTV 1200, and Parapac 200D. Manufacturer specifications for each ventilator were reviewed and compared with known standards for alarms and functionality for surge capacity ventilators. The delivered tidal volume, gas flow characteristics, and airway pressure waveforms were evaluated in vitro using a mechanical test lung to model pediatric lung injury and integrated software. Test lung and flow meter recordings were analyzed over a range of ventilator settings. Of the six ventilators assessed, only two had the minimum recommended alarm capability. Four of the six ventilators tested were capable of being set to deliver a tidal volume of less than 200 mL. The delivered tidal volume for all ventilators was within 8% of the nominal setting at a positive end expiratory pressure of zero but was reduced significantly with the addition of positive end expiratory pressure (range, ±10% to 30%; p < .01). All ventilators tested performed comparably at higher set tidal volumes; however, only three of the ventilators tested delivered a tidal volume across the range of ventilator settings that was comparable to that of a standard intensive care unit ventilator. CONCLUSIONS: Multiple ventilators are available for the provision of ventilation to children with respiratory failure in a mass casualty scenario. Few of these ventilators possess the minimum alarm functionality and consistently deliver the prescribed tidal volume that allows for safe and effective ventilation of critically ill pediatric patients. These findings will help clinicians understand the performance and limitations of available ventilators intended for use in children.

Monitoring cerebral blood flow pressure autoregulation in pediatric patients during cardiac surgery.

BACKGROUND AND PURPOSE: The limits of cerebral blood flow-pressure autoregulation have not been adequately defined for pediatric patients. Mean arterial blood pressure below these limits might contribute to brain injury during cardiac surgery. The purpose of this pilot study was to assess a novel method of determining the lower limits of pressure autoregulation in pediatric patients supported with cardiopulmonary bypass. METHODS: A prospective, observational pilot study was conducted in children (n=54) undergoing cardiac surgery with cardiopulmonary bypass for correction of congenital heart defects. Cerebral oximetry index (COx) was calculated as a moving, linear correlation coefficient between slow waves of arterial blood pressure and cerebral oximetry measured with near-infrared spectroscopy. An autoregulation curve was constructed for each patient with averaged COx values sorted by arterial blood pressure. RESULTS: Hypotension was associated with increased values of COx (P<0.0001). For 77% of patients, an individual estimate of lower limits of pressure autoregulation could be determined using a threshold COx value of 0.4. The mean lower limits of pressure autoregulation for the cohort using this method was 42+/-7 mm Hg. CONCLUSIONS: This pilot study of COx monitoring in pediatric patients demonstrates an association between hypotension during cardiopulmonary bypass and impairment of autoregulation. The COx may be useful to identify arterial blood pressure-dependent limits of cerebral autoregulation during cardiopulmonary bypass. Larger trials with neurological outcomes are indicated.

Effects of acid aspiration-induced acute lung injury on kidney function.

Acute lung injury (ALI) in combination with acute kidney injury carries a mortality approaching 80% in the intensive care unit. Recently, attention has focused on the interaction of the lung and kidney in the setting of ALI and mechanical ventilation (MV). Small animal models of ALI and MV have demonstrated changes in inflammatory mediators, water channels, apoptosis, and function in the kidney early in the course of injury. The purpose of this investigation was to test the hypothesis that ALI and injurious MV cause early, measurable changes in kidney structure and function in a canine HCl aspiration model of ALI when hemodynamics and arterial blood gas tensions are carefully controlled. Intratracheal HCl induced profound ALI as demonstrated by increased shunt fraction and airway pressures compared with sham injury. Sham-injured animals had similar mean arterial pressure and arterial Pco(2) and HCO(3) levels compared with injured animals. Measurements of renal function including renal blood flow, urine flow, serum creatinine, glomerular filtration rate, urine albumin-to-creatinine ratio, and kidney histology scores were not different between groups. With maintenance of hemodynamic parameters and alveolar ventilation, ALI and injurious MV do not alter kidney structure and function early in the course of injury in this acid aspiration canine model. Kidney injury in large animal models may be more similar to humans and may differ from results seen in small animal models.

Recombinant activated factor VII (rFVIIa) treatment in infants with hemorrhage.

BACKGROUND: Recombinant activated factor VII (rFVIIa) is approved by the FDA for the treatment of bleeding episodes in patients with hemophilia A or B with inhibitors to factor VIII or factor IX. In addition to the FDA-approved indications, rFVIIa has been anecdotally reported effective for profound bleeding episodes in adult patients without hemophilia, and proven beneficial for adults with intracranial hemorrhage. In the pediatric literature, case reports have been made with apparent clinical improvement seen after the use of rFVIIa for acute life-threatening bleeding; however, there are limited data regarding its use in infants<4 months of age. We report our experience with rFVIIa in nine infants with severe hemorrhage of diverse etiologies. METHODS: This case series of infants under 4 months with coagulopathy and bleeding treated with rFVIIa was collected from two institutions. We report the age, weight and pre-rFVIIa laboratory values of the patients as well as the clinical scenario and outcomes. RESULTS: The nine infants all suffered acute life-threatening hemorrhage. Two patients were postoperative from cardiac surgery, two with Vitamin K deficiency and intracranial hemorrhage, three with suspected necrotizing enterocolitis and abdominal hemorrhage, and two with pulmonary hemorrhage. The patients ranged in age from 2 days to 4 months, (average age 1 month and average weight 3.3+/-1.0 kg). Seven of the nine patients had frozen plasma, cryoprecipitate, or platelet administration in failed attempts to correct the coagulation defect prior to receiving rFVIIa. The dose range used in this series was 90-100 microg.kg-1, with 90 microg.kg-1 being the most commonly used dose. The average pre-rFVIIa INR was 8.7+/-5.1. Four patients had an immeasurably high INR. All patients had clinical resolution of bleeding after receiving rFVIIa, and seven of nine patients survived. CONCLUSIONS: rFVIIa is a powerful hemostatic drug whose mechanism of action provides a theoretical specificity to sites of tissue injury. In addition to its FDA-approved uses in hemophiliac patients, this drug has a potential role in the treatment of life-threatening hemorrhage from multiple causes.

Mechanism of hypoxemia in acute lung injury evaluated by multidetector-row CT.

RATIONALE AND OBJECTIVES: Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism causing pulmonary arterial constriction in response to local hypoxia, redistributing blood flow to lung regions with better oxygenation and ventilation. We present the use of computed tomographic (CT) volume and perfusion imaging to show differences in the mechanisms of hypoxemia from alterations in blood flow distribution within different animal models of acute lung injury (ALI). MATERIALS AND METHODS: Three anesthetized, instrumented, and ventilated sheep were studied, two with induced ALI and one with native pneumonia. One subject was injured by using intravenous infusion of lipopolysaccharide (LPS), and the other, by repetitive saline lavage. Subjects were imaged using multidetector-row CT (MDCT) before and after injury. Lung volume scans were gated to the respiratory cycle. Contrast injection perfusion images were electrocardiogram gated. Computer-based image analysis quantified regional blood flow and total lung, air, and tissue volumes. RESULTS: Total lung air fraction was decreased in both ALI models. In lavage injury, there was a decrease in perfusion to dependent poorly aerated regions, with perfusion shifting to nondependent regions. Conversely, LPS injury greatly increased perfusion to dependent poorly aerated regions. In the subject with pneumonia, decreasing fraction of inspired oxygen redistributed blood flow into the injured regions. CONCLUSIONS: MDCT techniques can be used to investigate regional lung perfusion and lung volume distributions to explain physiological mechanisms in ALI. Our findings suggest that after lavage injury, blood flow is redistributed, consistent with preserved HPV and resulting in better oxygenation despite greater lung volume loss compared with LPS injury. In native pneumonia, HPV inactivation can be localized to the injured regions.