Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement.

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

Pediatric brain death determination.

Clinical guidelines for the determination of brain death in children were first published in 1987. These guidelines were revised in 2011 under the auspices of the Society of Critical Care Medicine, the American Academy of Pediatrics, and the Child Neurology Society, and provide the minimum standards that must be satisfied before brain death can be declared in infants and children. After achieving physiologic stability and exclusion of confounders, two examinations including apnea testing separated by an observation period (24 hours for term newborns up to 30 days of age, and 12 hours for infants and children from 31 days up to 18 years) are required to establish brain death. Apnea testing should demonstrate a final arterial PaCO2 20 mm Hg above the baseline and ≥ 60 mm Hg with no respiratory effort during the testing period. Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. The committee concluded that ancillary studies may be used (1) when components of the examination or apnea testing cannot be completed, (2) if uncertainty about components of the neurologic examination exists, (3) if a medication effect may be present, or (4) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should still be performed and components that can be completed must remain consistent with brain death.

Effect of high-dose continuous albuterol nebulization on clinical variables in children with status asthmaticus.

OBJECTIVES: Continuous albuterol nebulization is generally administered at 2.5-20 mg/hr at most centers. We examined the effect of high-dose (75 or 150 mg/hr) albuterol on clinical variables in children with status asthmaticus. DESIGN: Retrospective analysis of inpatient medical records and prospectively collected computerized PICU respiratory therapy database. SETTING: Twenty-five-bed multidisciplinary PICU in a tertiary care children's hospital. PATIENTS: Children admitted to the PICU between January 2006 and December 2007 with status asthmaticus receiving high-dose continuous albuterol nebulization. (Those with cerebral palsy, cardiac pathology, and ventilator dependence were excluded.) INTERVENTIONS: : Chart review for PICU length of stay, albuterol dose, duration of nebulization, occurrence of chest pain, vomiting, tremors, hypokalemia (serum potassium < 3.0 mEq/L), and cardiac arrhythmia. Maximal heart rate, lowest diastolic blood pressure, and mean arterial pressure were compared to the variables at initiation of therapy and at hospital discharge. MEASUREMENTS AND MAIN RESULTS: Forty-two patients (22 boys and 20 girls) received high-dose continuous albuterol nebulization. Twenty-three received 75 mg/hr and 19 received 150 mg/hr (3.7 mg/kg/hr [interquartile range, 2.4-5.8 mg/kg/hr]) for a duration of 22.3 hours (interquartile range, 6.6-31.7 hr). Heart rate increased and diastolic blood pressure and mean arterial pressure were significantly lower during nebulization compared to initiation of therapy or at hospital discharge (p < 0.05). No patient required fluid resuscitation or inotropic support, and one had self-limited premature ventricular contractions. Hypokalemia occurred in five of 33 patients who had serum electrolytes measured but did not require supplementation. One patient required endotracheal intubation after initiation of nebulization, and seven patients (16.7%) received noninvasive ventilation. PICU length of stay was 2.3 ± 1.7 days; there were no deaths. CONCLUSIONS: High-dose continuous albuterol nebulization is associated with a low rate of subsequent mechanical ventilation and fairly short PICU length of stay without significant toxicity. Prospective studies comparing conventional and high-dose albuterol nebulization are needed to determine the optimum dose providing maximum efficacy with the least adverse effects.

Circulatory death determination in uncontrolled organ donors: a panel viewpoint.

One barrier for implementing programs of uncontrolled organ donation after the circulatory determination of death is the lack of consensus on the precise moment of death. Our panel was convened to study this question after we performed a similar analysis on the moment of death in controlled organ donation after the circulatory determination of death. We concluded that death could be determined by showing the permanent or irreversible cessation of circulation and respiration. Circulatory irreversibility may be presumed when optimal cardiopulmonary resuscitation efforts have failed to restore circulation and at least a 7-minute period has elapsed thereafter during which autoresuscitation to restored circulation could occur. We advise against the use of postmortem organ support technologies that reestablish circulation of warm oxygenated blood because of their risk of retroactively invalidating the required conditions on which death was declared.

Guidelines for the determination of brain death in infants and children: an update of the 1987 task force recommendations-executive summary.

OBJECTIVE: To review and revise the 1987 pediatric brain death guidelines. METHODS: Relevant literature was reviewed. Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. CONCLUSIONS AND RECOMMENDATIONS: (1) Determination of brain death in term newborns, infants, and children is a clinical diagnosis based on the absence of neurologic function with a known irreversible cause of coma. Because of insufficient data in the literature, recommendations for preterm infants <37 weeks gestational age are not included in these guidelines. (2) Hypotension, hypothermia, and metabolic disturbances should be treated and corrected, and medications that can interfere with the neurologic examination and apnea testing should be discontinued allowing for adequate clearance before proceeding with these evaluations. (3) Two examinations including apnea testing with each examination separated by an observation period are required. Examinations should be performed by different attending physicians. Apnea testing may be performed by the same physician. An observation period of 24 hours for term newborns (37 weeks gestational age) to 30 days of age and 12 hours for infants and children (>30 days to 18 years) is recommended. The first examination determines the child has met the accepted neurologic examination criteria for brain death. The second examination confirms brain death based on an unchanged and irreversible condition. Assessment of neurologic function after cardiopulmonary resuscitation or other severe acute brain injuries should be deferred for 24 hours or longer if there are concerns or inconsistencies in the examination. (4) Apnea testing to support the diagnosis of brain death must be performed safely and requires documentation of an arterial PaCO(2) 20mmHg above the baseline and ≥60mmHg with no respiratory effort during the testing period. If the apnea test cannot be safely completed, an ancillary study should be performed. (5) Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. Ancillary studies may be used to assist the clinician in making the diagnosis of brain death (a) when components of the examination or apnea testing cannot be completed safely due to the underlying medical condition of the patient; (b) if there is uncertainty about the results of the neurologic examination; (c) if a medication effect may be present; or (d) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should be performed, and components that can be completed must remain consistent with brain death. In this instance, the observation interval may be shortened, and the second neurologic examination and apnea test (or all components that are able to be completed safely) can be performed at any time thereafter. (6) Death is declared when these above criteria are fulfilled.

Impact of the Updated Guideline for Pediatric Brain Death Determination on Current Practice.

Background: A guideline to determine pediatric brain death was updated in 2011. It is unknown how pediatric intensivists have accepted and adopted the revised guideline into clinical practice. Methods: We surveyed US pediatric critical care attending physicians July 2013 to September 2013 and February 2020 to May 2020. Brain death testing practices and utilization of the 2011 pediatric and neonatal brain death guideline were assessed. Results: The 2020 respondents found that the revised pediatric brain death guideline were useful in clinical practice (93.7% vs 83.3%, P = .0484) and provided more consistency and clarity (73.2% vs 63.1%, P = .0462) when compared to 2013 respondents. Conclusion: This study demonstrates that with defined criteria, survey participants reported increased clarity and consistency. Findings from our study indicate that in clinical practice there is no significant deviation from the minimum requirements to determine brain death in children as outlined in the 2011 guideline.

Guidelines for the determination of brain death in infants and children: an update of the 1987 Task Force recommendations.

OBJECTIVE: To review and revise the 1987 pediatric brain death guidelines. METHODS: Relevant literature was reviewed. Recommendations were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. CONCLUSIONS AND RECOMMENDATIONS: 1) Determination of brain death in term newborns, infants, and children is a clinical diagnosis based on the absence of neurologic function with a known irreversible cause of coma. Because of insufficient data in the literature, recommendations for preterm infants <37 wks gestational age are not included in this guideline. 2) Hypotension, hypothermia, and metabolic disturbances should be treated and corrected and medications that can interfere with the neurologic examination and apnea testing should be discontinued allowing for adequate clearance before proceeding with these evaluations. 3) Two examinations, including apnea testing with each examination separated by an observation period, are required. Examinations should be performed by different attending physicians. Apnea testing may be performed by the same physician. An observation period of 24 hrs for term newborns (37 wks gestational age) to 30 days of age and 12 hrs for infants and children (>30 days to 18 yrs) is recommended. The first examination determines the child has met the accepted neurologic examination criteria for brain death. The second examination confirms brain death based on an unchanged and irreversible condition. Assessment of neurologic function after cardiopulmonary resuscitation or other severe acute brain injuries should be deferred for ≥24 hrs if there are concerns or inconsistencies in the examination. 4) Apnea testing to support the diagnosis of brain death must be performed safely and requires documentation of an arterial Paco2 20 mm Hg above the baseline and ≥60 mm Hg with no respiratory effort during the testing period. If the apnea test cannot be safely completed, an ancillary study should be performed. 5) Ancillary studies (electroencephalogram and radionuclide cerebral blood flow) are not required to establish brain death and are not a substitute for the neurologic examination. Ancillary studies may be used to assist the clinician in making the diagnosis of brain death a) when components of the examination or apnea testing cannot be completed safely as a result of the underlying medical condition of the patient; b) if there is uncertainty about the results of the neurologic examination; c) if a medication effect may be present; or d) to reduce the interexamination observation period. When ancillary studies are used, a second clinical examination and apnea test should be performed and components that can be completed must remain consistent with brain death. In this instance, the observation interval may be shortened and the second neurologic examination and apnea test (or all components that are able to be completed safely) can be performed at any time thereafter. 6) Death is declared when these criteria are fulfilled.

The circulatory-respiratory determination of death in organ donation.

OBJECTIVE: Death statutes permit physicians to declare death on the basis of irreversible cessation of circulatory-respiratory or brain functions. The growing practice of organ donation after circulatory determination of death now requires physicians to exercise greater specificity in circulatory-respiratory death determination. We studied circulatory-respiratory death determination to clarify its concept, practice, and application to innovative circulatory determination of death protocols. RESULTS: It is ethically and legally appropriate to procure organs when permanent cessation (will not return) of circulation and respiration has occurred but before irreversible cessation (cannot return) has occurred because permanent cessation: 1) is an established medical practice standard for determining death; 2) is the meaning of "irreversible" in the Uniform Determination of Death Act; and 3) does not violate the "Dead Donor Rule." CONCLUSIONS: The use of unmodified extracorporeal membrane oxygenation in the circulatory determination of death donor after death is declared should be abandoned because, by restoring brain circulation, it retroactively negates the previous death determination. Modifications of extracorporeal membrane oxygenation that avoid this problem by excluding brain circulation are contrived, invasive, and, if used, should require consent of surrogates. Heart donation in circulatory determination of death is acceptable if proper standards are followed to declare donor death after establishing the permanent cessation of circulation. Pending additional data on "auto-resuscitation," we recommend that all circulatory determination of death programs should utilize the prevailing standard of 2 to 5 mins of demonstrated mechanical asystole before declaring death.

What is the normal intra-abdominal pressure in critically ill children and how should we measure it?

INTRODUCTION: The intravesical method has been validated and is considered the gold standard for indirect intra-abdominal pressure (IAP) measurements. In adults, a standard volume (25 mL) is instilled into the bladder to measure IAP. However, the optimal volume for accurate IAP measurements in children has not been well studied and using inappropriate volumes could give erroneous IAP readings. OBJECTIVE: To determine the normal IAP in critically ill children and the optimal volume for IAP measurement by the intravesical method in this population. DESIGN: Prospective observational study. SETTING: Tertiary pediatric intensive care unit. PATIENTS: Ninety-six mechanically ventilated children younger than 18 yrs of age with no clinical evidence of intra-abdominal hypertension. MEASUREMENTS AND RESULTS: Graduated volumes of normal saline in increments of 3-50 mL were instilled in the bladder via a urethral catheter. IAP was recorded by using the AbViser device (WolfeTory Medical, Inc., Salt Lake City, UT) with each instillation. A pressure-volume curve was generated for every patient, and the minimum and mean optimal volumes were determined from this curve. Data were analyzed by stratification of patients according to weights 0-10 kg, >10-20 kg, and >20-50 kg. Descriptive statistics was used for statistical analysis. Normal IAP for critically ill children was 7 +/- 3 and was similar in the different weight groups (p = .745). Although the mean optimal volume to measure accurate IAP was variable in the different weight groups, the minimum optimal volume was 3 mL irrespective of weight. CONCLUSIONS: Mean IAP in critically ill children is 7 +/- 3 mm Hg. The minimum optimal volume needed to accurately measure IAP by the intravesical method in children is 3 mL. We recommend that 3 mL be the standard instillation volume for IAP measurement by the intravesical method in children. IAP >10 mm Hg should be considered elevated in children.

Pediatric critical care nurses' perceptions, knowledge, and attitudes regarding organ donation after cardiac death.

OBJECTIVE: Donation after cardiac death (DCD) is being implemented nationwide in the United States to increase the number of organ donors. Pediatric critical care nurses (PCRNs) are key facilitators in the organ donation process. This study assesses their perception, level of knowledge, and understanding of DCD and the effect of an educational intervention. DESIGN: Anonymous questionnaire administered before and after an educational intervention. SETTING: Children's hospital with 39 pediatric and cardiac/transplant intensive care unit beds. SUBJECTS: PCRNs in these intensive care units. INTERVENTIONS: DCD education. MEASUREMENTS AND MAIN RESULTS: Response to the initial questionnaire was 93 of 123 (76%): 63% of PCRNs supported organ donation, 69% felt it gives meaning and worth to death, and 76% felt that it contributes positively to the donating family's grieving process. Ninety-five percent agreed that DCD patients have a right to pain medications, and 92% supported such medications even if they hasten death. However, 11% feared that the DCD donor feels pain and suffering. Fourteen percent felt that a 5-min observation period after asystole is insufficient to pronounce death, and 8% feared legal repercussions. PCRNs scored lower on questions assessing their knowledge (p < .01), their comfort answering family questions (p < .05), and their comfort in calling the organ procurement agency about DCD donors compared with similar questions about brain-dead donors. One month after 104 PCRNs attended the educational intervention, 64 (62%) completed a follow-up survey. Correct identification of the DCD process improved from 20% to 79%. Confidence with knowledge, comfort answering family questions, and comfort in calling the organ procurement agency about DCD donors improved by 41%, 25%, and 18%, respectively. CONCLUSIONS: PCRNs are generally supportive of organ donation but have a self-perceived and objectively identified knowledge deficit regarding DCD, resulting in their being unprepared to identify potential DCD donors or handle family questions. A simple educational intervention can improve PCRNs' knowledge of the DCD process and their confidence and comfort with this process. As DCD policies are implemented, specific interventions should target these key members of the intensive care unit team.

Pediatric cardiac arrest due to drowning and other respiratory etiologies: Neurobehavioral outcomes in initially comatose children.

AIM: To describe the 1-year neurobehavioral outcome of survivors of cardiac arrest secondary to drowning, compared with other respiratory etiologies, in children enrolled in the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial. METHODS: Exploratory analysis of survivors (ages 1-18 years) who received chest compressions for ≥2min, were comatose, and required mechanical ventilation after return of circulation (ROC). Participants recruited from 27 pediatric intensive care units in North America received targeted temperature management [therapeutic hypothermia (33°C) or therapeutic normothermia (36.8°C)] within 6h of ROC. Neurobehavioral outcomes included 1-year Vineland Adaptive Behavior Scales, Second Edition (VABS-II) total and domain scores and age-appropriate cognitive performance measures (Mullen Scales of Early Learning or Wechsler Abbreviated Scale of Intelligence). RESULTS: Sixty-six children with a respiratory etiology of cardiac arrest survived for 1-year; 60/66 had broadly normal premorbid functioning (VABS-II≥70). Follow up was obtained on 59/60 (30 with drowning etiology). VABS-II composite and domain scores declined significantly from premorbid scores in drowning and non-drowning groups (p<0.001), although declines were less pronounced for the drowning group. Seventy-two percent of children had well below average cognitive functioning at 1-year. Younger age, fewer doses of epinephrine, and drowning etiology were associated with better VABS-II composite scores. Demographic variables and treatment with hypothermia did not influence neurobehavioral outcomes. CONCLUSIONS: Risks for poor neurobehavioral outcomes were high for children who were comatose after out-of-hospital cardiac arrest due to respiratory etiologies; survivors of drowning had better outcomes than those with other respiratory etiologies.

Physician assistants as physician extenders in the pediatric intensive care unit setting-A 5-year experience.

OBJECTIVE: To describe the scope of practice and complementary role of physician assistants as physician extenders in the pediatric intensive care unit. DESIGN: Descriptive report of a 5-yr experience using a physician assistant-resident staffing model in comparison to the traditional resident-only coverage. SETTING: Six-bed pediatric intensive care unit at a tertiary care center subject to longstanding New York Hospital Code 405 restrictions on resident work hours. INTERVENTIONS: Orientation, training, credentialing, and evaluation of physician assistants. MEASUREMENTS AND MAIN RESULTS: New Accreditation Council for Graduate Medical Education regulations based on the longstanding New York Hospital Code 405 limit the number of resident hours worked per week. Our hospital employs physician assistants as physician extenders in the pediatric intensive care unit to enable regulatory compliance. Physician assistants were oriented for a period of 6 months to 1 yr to develop skill competencies, observe and learn pediatric intensive care unit practices and procedures, and complete credentialing to perform traditionally physician, nursing, and respiratory therapist functions. Physician assistants were then assigned to an independent but supervised patient care role similar to that of a resident physician. The impact of the physician assistant program was assessed by the attending physicians, and resident opinions were surveyed. CONCLUSIONS: Physician assistants play a complementary role as physician extenders in the pediatric intensive care unit, enabling compliance with New York state and Accreditation Council for Graduate Medical Education resident work hour regulations. Physician assistants perform similar tasks and activities as the pediatric intensive care unit residents and integrate well with them in enhancing bedside patient care. Over time, physician assistants provide additional direction to the residents by virtue of their familiarity with unit-specific policies and procedures and repetitive pediatric intensive care unit practice patterns. As multifunctional members of the health care team, they support nursing and respiratory therapy functions and improve the day-to-day functioning of the unit. The physician assistant serves as a key member of the pediatric intensive care unit transport team. Limitations observed include high job turnover rates among the physician assistants and confusion between their role as shift workers or professional employees.

Management of a large organized intraatrial catheter-tip thrombus in a child with acquired immunodeficiency syndrome using escalating tissue plasminogen activator infusions.

OBJECTIVES: To describe the dissolution of a large organized intraatrial catheter-tip thrombus using a novel aggressive dose escalation of tissue plasminogen activator infusion. DESIGN: Case report. SETTING: A six-bed pediatric intensive care unit (ICU) at a university hospital. PATIENT: An 8-yr-old with acquired immunodeficiency syndrome with a large organized intraatrial thrombus at the tip of an indwelling central venous catheter placed for total parenteral nutrition 2 months before presentation. INTERVENTION: Escalating dose of tissue plasminogen activator infusion. MEASUREMENTS: A large intraatrial catheter-tip thrombus (2.5 x 3 cm) was an incidental finding on an echocardiogram done to assess cardiac function. The thrombus occupied almost half the right atrial cavity and hit the tricuspid valve with each heartbeat without obstruction of tricuspid inflow. The catheter had no blood return from either lumen for >1 month. Protein C, protein S, and antithrombin III were normal, and factor V Leiden and prothrombin gene mutations were absent. Blood cultures were negative. Pediatric and cardiovascular surgeons recommended open-heart surgery as the safest option for catheter removal to avoid the risk of superior vena cava occlusion, vascular rupture, or embolization. A second opinion concurred. A trial of thrombolytic therapy with tissue plasminogen activator infusions was started at 0.1 mg/kg/hr for 6 hrs daily. No change in thrombus size was seen on a followup echocardiogram after 4 days. An aggressive dose escalation (0.15, 0.2, 0.25 mg/kg/hr for 6 hrs) was done over the next 5 days in an attempt to avoid open-heart surgery. Risks regarding disseminated intravascular coagulation and bleeding were presented to the parents. MAIN RESULTS: Followup echocardiogram on day 10 showed complete resolution of the thrombus. No changes in respiratory/hemodynamic status or oxygen saturation were observed. Studies for disseminated intravascular coagulation remained stable, and no clinical bleeding was seen. The catheter was safely removed surgically; pathology examination showed no residual thrombus. CONCLUSIONS: Prolonged infusion of tissue plasminogen activator in escalating doses was safe and effective in the management of a large intracardiac catheter-tip thrombus and helped avoid open-heart surgery. In view of the potential hazards of tissue plasminogen activator, close pediatric ICU monitoring is indicated with the use of high-dose tissue plasminogen activator infusions.