Sheri Crow

Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices

OBJECTIVE Pulsatile and nonpulsatile left ventricular assist devices are effective in managing congestive heart failure. Despite early evidence for clinical efficacy, the long-term impact of nonpulsatile flow on end-organ function remains to be determined. Our goal was to compare rates of gastrointestinal bleeding in nonpulsatile and pulsatile device recipients. METHODS In a retrospective review of 101 left ventricular assist device recipients (55 nonpulsatile, 46 pulsatile) from October 31, 2003, to June 1, 2007, at a single center, gastrointestinal bleeding was defined as guaiac-positive stool with hemoglobin drop requiring transfusion of at least 2 units of packed red blood cells. To assess bleeding risk outside the initial postoperative course, any patients with a device in place for 15 days or less was excluded. RESULTS Twelve nonpulsatile and 3 pulsatile left ventricular assist device recipients had gastrointestinal bleeding 16 days or longer after device implantation. The event rates were 63 events/100 patient-years for nonpulsatile devices and 6.8 events/100 patient-years for pulsatile devices (P = .0004). This difference persisted for bleeding occurring 31 days or longer after device implantation, with 46.5 events/100 patient-years for nonpulsatile devices versus 4.7 events/100 patient-years for pulsatile devices (P = .0028). Mortalities were similar between groups (15% nonpulsatile vs 17% pulsatile, P = .6965). CONCLUSION Patients with nonpulsatile left ventricular assist devices appear to have a higher rate of gastrointestinal bleeding events than do pulsatile left ventricular assist device recipients. Further prospective evaluation is needed to determine potential etiologies and strategies for reducing gastrointestinal bleeding in this population.

Acquired von Willebrand Syndrome in Continuous-Flow Ventricular Assist Device Recipients

BACKGROUND Bleeding is a major cause of morbidity in recipients of continuous-flow left ventricular assist devices (CF-LVAD). A better understanding of the impact of CF-LVAD support on the hemostatic profile is necessary to establish better strategies for anticoagulation therapy and risk assessment for bleeding complications. A prospective multicenter study was conducted to characterize von Willebrand factor (vWF) profiles in patients undergoing CF-LVAD implantation. METHODS Blood samples were collected before and after CF-LVAD implantation from 37 patients between July 2008 and April 2009 at Duke University and the University of Minnesota. Blood samples were analyzed for vWF, platelet and collagen-binding ability. The presence of high-molecular-weight (HMW) vWF multimers were detected through gel electrophoresis, and deficiency was graded on a scale of 0 (normal) to 3 (severe loss). RESULTS All 37 patients exhibited significant loss of HMW vWF multimers within 30 days of CF-LVAD implantation. Ten of the 37 patients experienced bleeding complications after CF-LVAD placement. CONCLUSIONS All CF-LVAD recipients had acquired von Willebrand syndrome after LVAD placement, demonstrated by reduced or absent HMW vWF multimer levels. However, not all recipients had bleeding complications. These findings suggest that loss of HMW vWF multimers alone cannot predict bleeding risk. Further refinement of laboratory techniques and a larger follow-up is required to identify risk factors for bleeding in CF-LVAD recipients.

Mechanical circulatory support in patients with heart failure secondary to transposition of the great arteries

Advances in palliation of congenital heart disease have resulted in improved survival to adulthood. Many of these patients ultimately develop end-stage heart failure requiring left ventricular assist device implantation (LVAD). However, morphologic differences in the systemic ventricle of these patients require careful attention to cannula placement. We report on the evolution of our surgical technique for implanting LVADs in 3 patients with transposition of the great arteries and congenitally corrected transposition of the great arteries. Applying standard LV cannulation techniques to the systemic ventricle led us too anteriorly in our first patient, creating obstruction by the moderator band. Subsequent use of epicardial and transesophageal echocardiography allowed for intraoperative localization of the intracardiac muscular structures to identify the optimal cannulation site. The acute angle of the inflow cannula on the DeBakey LVAD (MicroMed Technology, Houston, TX) required flipping the device 180°. The HeartMate II device (Thoratec, Pleasanton, CA) could be shifted towards the midline. One patient underwent successful transplant and 2 are home waiting for a donor organ. We conclude from our experience that LVAD surgery can be safely performed in patients with congenital heart disease when implanted under echocardiographic guidance.

Comparative analysis of von Willebrand factor profiles in pulsatile and continuous left ventricular assist device recipients.

A higher rate of nonsurgical bleeding has been observed in nonpulsatile left ventricular assist device (LVAD) recipients. von Willebrand factor (vWF) profiles were compared for nonpulsatile and pulsatile LVAD recipients to explore mechanisms that may contribute to the development of postimplant nonsurgical bleeding. The nonpulsatile mechanism may impair vWF function by creating a deficiency in vWF high molecular weight multimers (HMWMs), essential for hemostasis. High molecular weight multimer deficiency should result in low ristocetin cofactor (RCo) to vWF antigen ratios (vWF:RCo/vWF:Ag) because of impaired platelet (plt)-binding ability. von Willebrand factor profiles and HMWM were measured pre- and post-LVAD placement in 11 nonpulsatile (HeartMate II [HM II[) and 3 pulsatile (HeartMate XVE [HM XVE]) recipients. All the nonpulsatile LVAD recipients exhibited loss of HMWM 30 days postimplant. The vWF:RCo/vWF:Ag ratio was significantly lower after LVAD placement in the nonpulsatile group when compared with the pulsatile group. In addition, the vWF:RCo/vWF:Ag ratio decreased significantly from baseline 30 days postimplant within the nonpulsatile recipients. All nonpulsatile LVAD recipients had low vWF:RCo/vWF:Ag ratios 30 days post-LVAD even if the values were normal at baseline. These data suggest that nonpulsatile HM II recipients develop HMWM loss and impaired vWF platelet (plt)-binding ability after LVAD placement. Similar results were not observed in our small series of pulsatile HM XVE recipients. This finding could suggest a contributing factor to the increase in nonsurgical bleeding observed in nonpulsatile LVAD patients. Further investigation is ongoing to identify specific causes of vWF impairment.

Existing data analysis in pediatric critical care research

Our objectives were to review and categorize the existing data sources that are important to pediatric critical care medicine (PCCM) investigators and the types of questions that have been or could be studied with each data source. We conducted a narrative review of the medical literature, categorized the data sources available to PCCM investigators, and created an online data source registry. We found that many data sources are available for research in PCCM. To date, PCCM investigators have most often relied on pediatric critical care registries and treatment- or disease-specific registries. The available data sources vary widely in the level of clinical detail and the types of questions they can reliably answer. Linkage of data sources can expand the types of questions that a data source can be used to study. Careful matching of the scientific question to the best available data source or linked data sources is necessary. In addition, rigorous application of the best available analysis techniques and reporting consistent with observational research standards will maximize the quality of research using existing data in PCCM.

An unusual presentation of a congenital intrahepatic arterioportal fistula in an infant with Down syndrome

Congenital intrahepatic arterioportal fistula is a rare entity that most often presents with symptoms of portal hypertension and malabsorption. We discuss a patient who presented with distributive shock, congestive heart failure, pulmonary hypertension, ascites, and a history of severe constipation.

Epidemiology and Outcomes of Pediatric Multiple Organ Dysfunction Syndrome.

Objective: To summarize the epidemiology and outcomes of children with multiple organ dysfunction syndrome as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development multiple organ dysfunction syndrome workshop (March 26–27, 2015). Data Sources: Literature review, research data, and expert opinion. Study Selection: Not applicable. Data Extraction: Moderated by an experienced expert from the field, issues relevant to the epidemiology and outcomes of children with multiple organ dysfunction syndrome were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Data Synthesis: Summary of presentations and discussion supported and supplemented by the relevant literature. Conclusions: A full understanding the epidemiology and outcome of multiple organ dysfunction syndrome in children is limited by inconsistent definitions and populations studied. Nonetheless, pediatric multiple organ dysfunction syndrome is common among PICU patients, occurring in up to 57% depending on the population studied; sepsis remains its leading cause. Pediatric multiple organ dysfunction syndrome leads to considerable short-term morbidity and mortality. Long-term outcomes of multiple organ dysfunction syndrome in children have not been well studied; however, studies of adults and children with other critical illnesses suggest that the risk of long-term adverse sequelae is high. Characterization of the long-term outcomes of pediatric multiple organ dysfunction syndrome is crucial to identify opportunities for improved treatment and recovery strategies that will improve the quality of life of critically ill children and their families. The workshop identified important knowledge gaps and research priorities intended to promote the development of standard definitions and the identification of modifiable factors related to its occurrence and outcome.

Dexamethasone levels predict cortisol response after infant cardiopulmonary bypass

OBJECTIVES We sought to evaluate whether there is variability in blood dexamethasone levels after a standard 1 mg/kg dose of dexamethasone administered before infant cardiopulmonary bypass. We hypothesized that postoperative dexamethasone drug levels are highly variable, and that the infant stress response is related inversely to the amount of dexamethasone measured in the blood. METHODS Thirty-two infants (age, ≤365 days) received 1 mg/kg of dexamethasone before cardiopulmonary bypass (CPB) initiation. Blood was analyzed for cortisol, adrenocorticotropin, and interleukin (IL)-6, IL-8, and IL-10 levels after anesthesia induction, after CPB, after intensive care unit (ICU) arrival, and 4, 8, 12, and 24 hours after surgery. Patients were grouped as high dexamethasone (≥15 μg/dL) or low dexamethasone (<15 μg/dL) based on their level at ICU arrival. RESULTS Dexamethasone levels varied significantly between the high (n = 22) and low (n = 10) dexamethasone groups throughout the entire postoperative course and were correlated highly with cortisol response. Patients with high dexamethasone levels had postoperative cortisol levels that were lower than their pre-CPB baseline cortisol levels. Cortisol levels remained low throughout the first 24 postoperative hours even after dexamethasone levels neared zero. There were no significant differences between groups in the duration of mechanical ventilation or ICU length of stay. CONCLUSIONS Dexamethasone levels are highly variable at ICU arrival, despite standardized 1 mg/kg dosing before CPB initiation.

Epidemiology of Pediatric Critical Illness in a Population-Based Birth Cohort in Olmsted County, MN

Objectives: Investigations of pediatric critical illness typically focus on inpatient cohorts drawn from wide referral areas and diverse healthcare systems. Cohorts amenable to investigating the full spectrum of critical illness as it develops within a community have yet to be studied in the United States. Our objective was to provide the first epidemiologic report of the incidence and presentation of pediatric critical illness within a U.S. population-based birth cohort. Design: Retrospective cohort study. Setting: A geographically defined community (Olmsted, MN) with medical record linkage across all health systems. All ICU services are provided within a single children’s hospital. Patients: A birth cohort of children (n =9,441) born 2003–2007 in Olmsted County, MN. Measurements and Main Results: During the study period, there were a total of 15,277 ICU admissions to Mayo Clinic Children’s Hospital. A total of 577 birth cohort children accounted for 824 of these admissions during the 61,770 person-years of follow-up accumulated. Incidence of first-time ICU admission was 9.3 admits per 1,000 person-years. Admission rates were highest in the first year of life and then declined steadily. Respiratory problems were among the most common reasons for admission at any age and diagnoses reflect changes in health risk factors as children grow and develop over time. After 1 year old, a majority of children admitted have preexisting chronic comorbidities and/or prior ICU stays. In-hospital mortality occurred exclusively in children admitted prior to 5 days of age (n = 4). Seven children died after hospital discharge. Conclusions: This is the first report characterizing critical illness within a population-based birth cohort of U.S. children. The results demonstrate the changing incidence, presentation, and healthcare requirements associated with critical illness across the developmental spectrum as a population of children ages.

Life after Critical Illness in Children—Toward an Understanding of Pediatric Post-intensive Care Syndrome

C ritical illness is a life-changing event for patients and their families. As mortality has declined, many survivors experience new and persistent impairments in physical, psychological, cognitive, and social functioning. In adults, new morbidities are prevalent and often severe, and can persist years after the individual leaves the intensive care unit (ICU). Family members are also affected, as morbidities create challenges in supporting a loved one through convalescence and influence that person’s own quality of life. These collective problems, that is, new or worsening impairment in physical, cognitive, or mental health arising after critical illness and persisting beyond acute care hospitalization have been well described in adult survivors of intensive care and are now commonly referred to as post-intensive care syndrome (PICS) and PICS family. Studies of PICS in pediatric ICU (PICU) survivors are limited, but data are accumulating that many children develop significant, long-lasting morbidities similar to those observed in adults. However, additional factors specific to child health are crucial, including the child’s capacity and need for growth and development, the integral role of the family, and the potential impact on the child’s lifetime trajectory. The dynamic nature of development includes periods of vulnerability during which injuries may alter development into adulthood. Thus, new functional and cognitive impairments may affect a cascade of developmental milestones, school performance, and social interactions, placing a child at risk for a multitude of problems later in life. Conversely, the child’s capacity for growth may be a source of resilience that provides a platform for recovery after critical illness. The psychosocial and family effects of PICS are also different for the pediatric population. Children live in a social milieu primarily organized around family and school, which may confer resilience or expose vulnerabilities in response to illness or injury. The effects of pediatric critical illness on parents are different due to the unique nature of the parent-child relationship, an “inseparable dyad,” which has its own influence on child outcomes. Sibling relationships can also play a protective role in a child’s response to stressful events. However, siblings themselves may experience stress, loss of parental attention, and increased responsibilities related to the child’s critical illness, with unknown long-term impact. We review the current state of what is known about pediatric PICS (PICS-p). We also present areas of uncertainty and key knowledge gaps. Recognizing the central role that growth, development, and family relationships play in the association between pediatric illness and outcomes, we center our discussions using a recently described pediatric-specific PICS framework (Figure) that will support urgently needed research for children surviving critical illness and their families.