Dosing of medications is based on the plasma level achieved with a given dose and how long the medicine remains in the body. This study is called pharmacokinetics-that is, what the body does to the medication. Ketamine is an intravenous medication used for anesthesia and sedation in children. However the pharmacokinetics of Ketamine has not been systematically studied. We propose to study the pharmacokinetics of ketamine in different age groups of children ranging from infants to teenagers.
Stanford is currently not accepting patients for this trial. For more information, please contact Archana Verma, (650) 721 - 1713.
The investigators hope to learn 1) if the addition of prophylaxis with vancomycin will decrease the rate of cefazolin non-susceptible surgical site infections (SSI), in high risk population 2) to develop better understanding of vancomycin and cefazolin pharmacokinetics in children undergoing cardiopulmonary bypass (CPB) 3) to assess the barriers to vancomycin dosing peri-operatively 4) to assess side effects and risks associated with peri-operative vancomycin administration. This will allow us to improve patient care by better understanding the benefits or the risks of peri-operative vancomycin administration and potentially decrease cefazolin-resistant surgical site infections. In addition, this study gives us the opportunity to evaluate cefazolin and vancomycin pharmacokinetics (pK) on children on CPB. The investigators will take blood samples from 20 patients. In 10 patients the investigators will do Cefazolin pK analysis and in the other 10 the investigators will do pK Vancomycin analysis. For the remainder of 292 patients, only prospective chart review will be done to determine the incidence of SSIs. This data will be compared with 936 controls who received only Cefazolin pre-operatively as prophylaxis for SSI's.
Stanford is currently not accepting patients for this trial. For more information, please contact Kathleen Gutierrez, MD, 650-736-7642.
The purpose of this study is to validate the Nonin Near-infrared spectroscopy (NIRS) device to measure regional oxygen saturation in a cohort of children with cardiovascular disease undergoing cardiac catheterization.
Stanford is currently not accepting patients for this trial. For more information, please contact Chandra Ramamoorthy, (650) 723 - 5728.
BACKGROUND: Ferumoxytol, an "off-label" contrast agent, allows for better cardiac MRI quality as compared with gadolinium-based contrast agents. However, hypotension has been reported with the use of ferumoxytol for indications other than cardiac MRI. The purpose of our investigation was to evaluate the safety of ferumoxytol in children undergoing general anaesthesia for cardiac MRI.METHODS: Medical records of children undergoing general anaesthesia for cardiac MRI were reviewed. Baseline demographic and medical characteristics, as well as imaging and anaesthetic duration and technique, were collected. The incidence of hypotension or other adverse events', need for vasoactive support, or airway intervention throughout the anaesthetic, was recorded.RESULTS: A total of 95 patients were identified, 61 received ferumoxytol and 34 received gadolinium. There were no significant differences between groups with respect to age, weight, or baseline blood pressure. The incidence of low blood pressure - systolic or mean - after contrast administration did not differ between groups, and there was no difference in sustained hypotension or use of vasopressors between groups. One patient who received ferumoxytol had possible anaphylaxis. The image acquisition time (45 versus 68 min, p=0.002) and anaesthesia duration (100 versus 132 min, p=0.02) were shorter in the ferumoxytol group.CONCLUSION: Transient low blood pressure was common in children undergoing cardiac MRI with anaesthesia, but the incidence of hypotension did not differ between ferumoxytol and gadolinium groups. The use of ferumoxytol was associated with significantly shorter scan time and anaesthesia duration, as well as a decreased need for airway intervention.
As physicians and caregivers of children with congenital heart disease, we are aware of the increasing need for procedures requiring anesthesia. While these procedures may be ideal for medical and cardiac surgical management, the risks and benefits must be assessed carefully. There are well known risks of cardiovascular and respiratory complications from anesthesia and sedation and a potentially under-appreciated risk of neurocognitive dysfunction. Both animal and human studies support the detrimental effects of repeated anesthetic exposure on the developing brain. Although the studies in humans are less convincing of this risk, the Society of Pediatric Anesthesia jointly with SmartTots provided a consensus statement on the use of anesthetic and sedative drugs in infants and toddlers when speaking to families. (www.pedsanesthesia.org; http://smarttots.org/wp-content/uploads/2015/10/ConsensusStatementV910.5.2015.pdf). An excerpt of the statement is "Concerns regarding the unknown risk of anesthetic exposure to your child's brain development must be weighed against the potential harm associated with cancelling or delaying a needed procedure. Each child's care must be evaluated individually based on age, type, and urgency of the procedure and other health factors. This review provides a summary of the current evidence regarding anesthesia-induced neurotoxicity and the developing brain and its implications for children with congenital heart disease.
During a pulmonary hypertensive crisis, the marked increase in pulmonary vascular resistance can result in acute right ventricular failure and death. Currently, there are no therapeutic guidelines for managing an acute crisis. This pilot study examined the hemodynamic effects of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertension.In this prospective, open-label, nonrandomized pilot study, we enrolled pediatric patients previously diagnosed with pulmonary hypertensive who were scheduled electively for cardiac catheterization. Primary outcome was a change in the ratio of pulmonary-to-systemic vascular resistance. Baseline hemodynamic data were collected before and after the study drug was administered.Eleven of 15 participants were women, median age was 9.2 years (range, 1.7-14.9 yr), and median weight was 26.8 kg (range, 8.5-55.2 kg). Baseline mean pulmonary artery pressure was 49 ± 19 mm Hg, and mean indexed pulmonary vascular resistance was 10 ± 5.4 Wood units. Etiology of pulmonary hypertensive varied, and all were on systemic pulmonary hypertensive medications.Patients 1-5 received phenylephrine 1 μg/kg; patients 6-10 received arginine vasopressin 0.03 U/kg; and patients 11-15 received epinephrine 1 μg/kg. Hemodynamics was measured continuously for up to 10 minutes following study drug administration.After study drug administration, the ratio of pulmonary-to-systemic vascular resistance decreased in three of five patients receiving phenylephrine, five of five patients receiving arginine vasopressin, and three of five patients receiving epinephrine. Although all three medications resulted in an increase in aortic pressure, only arginine vasopressin consistently resulted in a decrease in the ratio of systolic pulmonary artery-to-aortic pressure.This prospective pilot study of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertensive showed an increase in aortic pressure with all drugs although only vasopressin resulted in a consistent decrease in the ratio of pulmonary-to-systemic vascular resistance. Studies with more subjects are warranted to define optimal dosing strategies of these medications in an acute pulmonary hypertensive crisis.
Prior studies have shown inaccuracies in pulse oximetry readings at saturations less than 85%; however, no large studies have evaluated new sensors marketed for these low saturations. This study's purpose was to evaluate two sensors with claims of improved accuracy in children with saturations less than 85%.Prospective observational study.Single institution; cardiac catheterization laboratory, and operating room.Fifty patients weighing 3-20 kg with baseline saturations less than 90% undergoing surgical or catheterization procedure.Data collected included demographics, diagnosis, continuous saturations from three different pulse oximeters (Masimo LNCS [Masimo, Irvine, CA], Masimo Blue [Masimo], and Nellcor Max-I [Medtronic, Dublin, Ireland]) and up to four blood samples for co-oximetry as the gold-standard arterial oxygen saturation. Analysis included scatter plots, smoothed regression estimates of mean continuous saturation levels plotted against corresponding arterial oxygen saturation values, and Bland-Altman plots. Bland-Altman analysis indicated increasing levels of bias and variability for decreasing arterial oxygen saturation levels for all three sensors, with a statistically significant increase in mean difference observed for decreasing arterial oxygen saturation level. The Masimo Blue sensor had the lowest mean difference, SD and Bland-Altman limits in patients with saturations less than or equal to 85%. At saturation range of less than or equal to 85% and greater than 75%, 14% of the samples obtained from Masimo Blue, 24% of the readings from the Nellcor, and 31% from the Masimo Standard sensors were greater than or equal to 5% points difference. All three sensors had a further increase in these differences for arterial oxygen saturation values less than 75%.The Masimo Blue sensor has improved accuracy at saturations 75-85% versus the Nellcor and Masimo Standard sensors. The accuracy of peripheral capillary oxygen saturation of the Masimo Blue sensor was within 5% points of the arterial oxygen saturation the majority of the time. Currently, at saturations less than or equal to 85%, pulse oximetry alone should not be relied on in making clinical decisions.
Prior investigations have suggested that the rapidly growing population of adults with congenital heart disease is at increased risk of perioperative morbidity and mortality, but information is limited on the nature of those perioperative factors that may relate to adverse outcomes. We sought to use a national claims database to describe the contribution of perioperative factors to adverse outcomes and compare contributing factors in cardiac vs. noncardiac operations.The study is a retrospective in-depth structured analysis of cases from the Anesthesia Closed Claims Project database.We examined the largest national anesthesia malpractice claims database.We included all claims cases involving adult patients with congenital heart disease (CHD).Patients in this retrospective analysis were classified by type of surgery (cardiac or noncardiac).Perioperative factors contributing to an adverse event were assessed by an expert panel of cardiac anesthesiologists.Of 21 confirmed cases, 11 (52%) involved cardiac procedures and 10 (48%) noncardiac procedures. The most common factors contributing to the adverse event in cardiac cases were surgical technique (73% of cases) and intraoperative anesthetic care (55%), whereas in noncardiac cases, postoperative monitoring/care (50%), CHD (50%) and preoperative assessment or optimization (40%) were most common. The factors contributing to the patient injury differed similarly: in cardiac cases, the most common factors were intraoperative anesthetic care (55%) and surgical technique (45%) compared with postoperative monitoring/care (50%) and CHD (50%) in noncardiac cases.Within the limitations of a small number of events in a claims-based database, this study offers advantages of being a national, structured analysis of real cases to provide detailed information on phenomena that are otherwise abstract and hypothesized by expert opinion. These results should help affirm the role of anesthesiologists in acquiring and executing expertise as consultants in perioperative medicine for adults with congenital heart disease patients.
BACKGROUND: From 2002 to 2005, the interstage mortality after a modified Norwood procedure was 7% in our program. An interstage home monitoring program (HMP) was established to identify Norwood procedure patients at increased risk of decompensation and to reduce interstage mortality. METHODS: Results of the first 5 years of the Norwood HMP were reviewed retrospectively. Interstage was defined as the time between Norwood hospital discharge and admission for second stage surgical palliation. In the HMP, families documented oxygen saturation, heart rate, weight, and feedings daily. Nurse practitioners called each family at least weekly, and when issues arose, action plans were determined based on symptom severity. RESULTS: Between October 2005 and October 2010 there were 46 Norwood procedure patients who survived to hospital discharge. All were enrolled in the HMP. Forty-five patients had a Norwood procedure with right ventricle to pulmonary artery conduit, and 1 patient had a modified Blalock-Taussig shunt. Interstage survival was 100%. Nineteen patients (41%) were admitted interstage; 5 patients were admitted twice, 1 patient was admitted 4 times. Seventeen patients (37%) required interstage interventions. Eight patients (17%) required major interventions: conduit stenting, aortic arch balloon angioplasty, emergent shunt, or early Glenn surgery. Minor interventions included supplemental oxygen, blood transfusion, intravenous hydration, diuresis, anti-arrhythmic therapy, or feeding adjustments. CONCLUSIONS: In the first 5 years of the HMP, all infants discharged after a modified Norwood procedure survived the interstage period. The HMP altered clinical management in 37% of patients. Home monitoring of oxygen saturation, heart rate, weight, and feedings, along with comprehensive care coordination, allowed timely interventions and reduced interstage mortality from 7% to 0%.
Home monitoring program reduces interstage mortality after the modified Norwood procedure JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Siehr, S. L., Norris, J. K., Bushnell, J. A., Ramamoorthy, C., Reddy, V. M., Hanley, F. L., Wright, G. E. 2014; 147 (2): 718-?
OBJECTIVE: To examine the knowledge and attitudes of anesthesia providers in relation to the care of adult congenital heart disease (ACHD) patients presenting for noncardiac surgery. DESIGN/SETTING: A novel survey was designed and administered to 168 anesthesiologists across a single academic department in a range of practice environments. INTERVENTIONS: None. OUTCOME MEASURES: Survey responses, including true/false, multiple choice, and Likert scale questions. RESULTS: A total of 118 anesthesiologists (response rate = 70%) completed the survey. Knowledge scores ranged from 0 to 19 (median [interquartile range] = 7 [5-13]) out of a possible maximum of 20. Total knowledge scores differed significantly by fellowship background (P = .004), with higher scores in those with cardiac (11 [7-15], P = .005) and pediatric (12 [6-15], P = .001) fellowship training, but not in those with critical care, obstetric, regional, or pain management training. Scores also differed by frequency of providing care for cardiopulmonary bypass cases and frequency of providing care for patients under 2 years of age (P < .001 for both), but not by gender or years removed from residency. Respondents reported only moderate levels of comfort with a range of questions about providing perioperative or obstetric care to ACHD patients, with decreasing levels of comfort reported in patients with more complex lesions. CONCLUSIONS: Within the context of the limitations of a single-institution survey design, the low levels of knowledge and comfort we observed suggest that providers may benefit from improved training and protocols for ensuring adequate preparedness for the care of ACHD patients.
: To describe volatile anesthesia (VA) use for pediatric asthma, including complications and outcomes.: Retrospective cohort study.: Children's hospitals contributing to the Pediatric Health Information System between 2004-2008.: Children 2-18 years old with a primary diagnosis code for asthma supported with mechanical ventilation.: Those treated with VA were compared to those not treated with VA or extracorporeal membrane oxygenation. Hospital VA use was grouped as none, <5%, 5-10% and >10% among intubated children.: One thousand five hundred and fifty-eight patients received mechanical ventilation at 40 hospitals for asthma: 47 (3%) received VA treatment at 11 (28%) hospitals. Those receiving a VA were significantly less likely to receive inhaled b-agonists, ipratropium bromide, and heliox, but more likely to receive neuromuscular blocking agents than patients treated without VA. Length of mechanical ventilation, hospital stay (length of stay [LOS]) and charges were significantly greater for those treated with VA. Aspiration was more common but death and air leak did not differ. Patients at hospitals with VA use >10% were significantly less likely to receive inhaled b agonist, ipratropium bromide, methylxanthines, and heliox, but more likely to receive systemic b agonist, neuromuscular blocking agents compared to those treated at hospitals not using VA. LOS, duration of ventilation, and hospital charges were significantly greater for patients treated at centers with high VA use.: Mortality does not differ between centers that use VA or not. Patients treated at centers with high VA use had significantly increased hospital charges and increased LOS.
Cerebral hypoxia-ischemia remains a complication in children with congenital heart disease. Near-infrared spectroscopy can be utilized at the bedside to detect cerebral hypoxia-ischemia. This study aimed to calibrate and validate an advanced technology near-infrared cerebral oximeter for use in children with congenital heart disease.After institutional review board approval and parental consent, 100 children less than 12 years and less than 40 kg were enrolled. Phase I (calibration) measured arterial and jugular venous saturation (SaO(2), SjO(2)) by co-oximetry simultaneously with device signals to calibrate an algorithm to determine regional cerebral saturation against a weighted average cerebral saturation (0.7 SjO(2) + 0.3 SaO(2)). Phase II (validation) evaluated regional cerebral saturation from the algorithm against the weighted average cerebral saturation by correlation, bias, precision, and A(Root Mean Square) assessed by linear regression and Bland-Altman analysis.Of 100 patients, 86 were evaluable consisting of 7 neonates, 44 infants, and 35 children of whom 55% were female, 79% Caucasian, and 41% with cyanotic disease. The SaO(2) and regional cerebral saturation ranged from 34% to 100% and 34% to 91%, respectively. There were no significant differences in subject characteristics between phases. For the entire cohort, A(RMS), bias, precision, and correlation coefficient were 5.4%, 0.5%, 5.39%, and 0.88, respectively. Age, skin color, and hematocrit did not affect these values.This cerebral oximeter accurately measures the absolute value of cerebral saturation in children over a wide range of oxygenation and subject characteristics, offering advantages in assessment of cerebral hypoxia-ischemia in congenital heart disease.
The incidence and prevalence of adolescent obesity and adolescent heart failure are increasing, and anesthesiologists increasingly will encounter patients with both conditions. A greater understanding of the physiologic challenges of adolescent heart failure as they relate to the perioperative stressors of anesthesia and bariatric surgery is necessary to successfully manage the perioperative risks faced by this growing subpopulation. Here, we present a representative case of a morbidly obese adolescent with heart failure who underwent a laparoscopic bariatric operation and review the limited available literature on perioperative management in this age group. Specifically, we review evidence and offer recommendations related to preoperative evaluation, venous thromboembolism prophylaxis, positioning, induction, airway management, monitoring, anesthetic maintenance, ventilator management, and adverse effects of the pneumoperitoneum, rhabdomyolysis, and postoperative care.
The aim of this study is to evaluate the effect of temperature on cerebral oxygen metabolism at total body flow bypass and antegrade cerebral perfusion (ACP). Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow rate of 200mL/kg/min. After cooling to 18°C (n=6) or 25°C (n=7), flow was reduced to 100mL/kg/min (half-flow, HF) for 15min and ACP was initiated at 40mL/kg/min for 45min. Following rewarming, animals were weaned from bypass and survived for 4h. At baseline, HF, ACP, and 4 h post-CPB, cerebral blood flow (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction (CEO(2) ) and cerebral metabolic rate of oxygen (CMRO(2) ) were monitored. Regional cranial oxygen saturation (rSO(2) ) was continuously recorded throughout the procedure using near-infrared spectroscopy. At 18°C, CBF trended lower at HF and ACP and matched baseline after CPB. CEO(2) trended lower at HF and ACP, and trended higher after CPB compared with baseline. CMRO(2) at ACP matched that at HF. Cranial rSO(2) was significantly greater at HF and ACP (P<0.001, P<0.001) and matched baseline after CPB. At 25°C, CBF trended lower at HF, rebounded and trended higher at ACP, and matched baseline after CPB. CEO(2) was equal at HF and ACP and trended higher after CPB compared with baseline. CMRO(2) at ACP was greater than that at HF (P=0.001). Cranial rSO(2) was significantly greater at HF (P=0.01), equal at ACP, and lower after CPB (P=0.03). Lactate was significantly higher at all time points (P=0.036, P<0.001, and P<0.001). ACP provided sufficient oxygen to the brain at a total body flow rate of 100mL/kg/min at deep hypothermia. Although ACP provided minimum oxygenation to the brain which met the oxygen requirement, oxygen metabolism was altered during ACP at moderate hypothermia. ACP strategy at moderate hypothermia needs further investigation.
From 1994 to 2005, the Pediatric Perioperative Cardiac Arrest Registry collected data on 373 anesthesia-related cardiac arrests (CAs) in children, 34% of whom had congenital or acquired heart disease (HD).Nearly 80 North American institutions that provide anesthesia for children voluntarily enrolled in the Pediatric Perioperative Cardiac Arrest Registry. A standardized data form for each perioperative CA in children 18 years old or younger was submitted anonymously. We analyzed causes of and outcomes from anesthesia-related CA in children with and without HD.Compared with the 245 children without HD, the 127 children with HD who arrested were sicker (92% vs 62% ASA physical status III-V; P < 0.01) and more likely to arrest from cardiovascular causes (50% vs 38%; P = 0.03), although often the exact cardiovascular cause of arrest could not be determined. Mortality was higher in patients with HD (33%) than those without HD (23%, P = 0.048) but did not differ when adjusted for ASA physical status classification. More than half (54%) of the CA in patients with HD were reported from the general operating room compared with 26% from the cardiac operating room and 17% from the catheterization laboratory. The most common category of HD lesion in patients suffering CA was single ventricle (n = 24). At the time of CA, most patients with congenital HD were either unrepaired (59%) or palliated (26%). Arrests in patients with aortic stenosis and cardiomyopathy were associated with the highest mortality rates (62% and 50%, respectively), although statistical comparison was precluded by small sample size for some HD lesions.Children with HD were sicker compared with those without HD at the time of anesthesia-related CA and had a higher mortality after arrest. These arrests were reported most frequently from the general operating room and were likely to be from cardiovascular causes. The identification of causes of and factors relating to anesthesia-related CA suggests possible strategies for prevention.
Antegrade cerebral perfusion is widely used in neonatal heart surgery, yet commonly used flow rates have never been standardized. The objective of this study was to determine the antegrade cerebral perfusion flow rate that most closely matches standard cardiopulmonary bypass conditions.Nine neonatal piglets underwent deep hypothermic cardiopulmonary bypass at a total body flow of 100 mL/kg/min (baseline). Antegrade cerebral perfusion was conducted via innominate artery cannulation at perfusion rates of 10, 30, and 50 mL/kg/min in random order. Cerebral blood flow was measured using fluorescent microspheres. Regional oxygen saturation and cerebral oxygen extraction were monitored.Cerebral blood flow was as follows: baseline, 60 +/- 17 mL/100 g/min; antegrade cerebral perfusion at 50 mL/kg/min, 56 +/- 17 mL/100 g/min; antegrade cerebral perfusion at 30 mL/kg/min, 36 +/- 9 mL/100 g/min; and antegrade cerebral perfusion at 10 mL/kg/min, 13 +/- 6 mL/100 g/min. At an antegrade cerebral perfusion rate of 50 mL/kg/min, cerebral blood flow matched baseline (P = .87), as did regional oxygen saturation (P = .13). Antegrade cerebral perfusion at 30 mL/kg/min provided approximately 60% of baseline cerebral blood flow (P < .002); however, regional oxygen saturation was equal to baseline (P = .93). Antegrade cerebral perfusion at 10 mL/kg/min provided 20% of baseline cerebral blood flow (P < .001) and a lower regional oxygen saturation than baseline (P = .011). Cerebral oxygen extraction at antegrade cerebral perfusion rates of 30 and 50 mL/kg/min was equal to baseline (P = .53, .48) but greater than baseline (P < .0001) at an antegrade cerebral perfusion rate of 10 mL/kg/min. The distributions of cerebral blood flow and regional oxygen saturation were equal in each brain hemisphere at all antegrade cerebral perfusion rates.Cerebral blood flow increased with antegrade cerebral perfusion rate. At an antegrade cerebral perfusion rate of 50 mL/kg/min, cerebral blood flow was equal to baseline, but regional oxygen saturation and cerebral oxygen extraction trends suggested more oxygenation than baseline. An antegrade cerebral perfusion rate of 30 mL/kg/min provided only 60% of baseline cerebral blood flow, but cerebral oxygen extraction and regional oxygen saturation were equal to baseline. An antegrade cerebral perfusion rate that closely matches standard cardiopulmonary bypass conditions is between 30 and 50 mL/kg/min.
Pulmonary arterial hypertension (PAH) is associated with significant perioperative risk for major complications in children, including pulmonary hypertensive crisis and cardiac arrest. Uncertainty remains about the safety of ketamine anesthesia in this patient population.Retrospectively review the medical records of children with PAH to ascertain the nature and frequency of peri-procedural complications and to determine whether ketamine administration was associated with peri-procedural complications.Children with PAH (mean pulmonary artery pressure > or =25 mmHg and pulmonary vascular resistance index > or =3 Wood units) who underwent general anesthesia for procedures during a 6-year period (2002-2008) were enrolled. Details about the patient, PAH, procedure, anesthetic and postprocedural course were noted, including adverse events during or within 48 h of the procedure. Complication rates were reported per procedure. Association between ketamine and peri-procedural complications was tested.Sixty-eight children (median age 7.3 year, median weight 22 kg) underwent 192 procedures. Severity of PAH was mild (23%), moderate (37%), and severe (40%). Procedures undertaken were major surgery (n = 20), minor surgery (n = 27), cardiac catheterization (n = 128) and nonsurgical procedures (n = 17). Ketamine was administered during 149 procedures. Twenty minor and nine major complications were noted. Incidence of cardiac arrest was 0.78% for cardiac catheterization procedures, 10% for major surgical procedures and 1.6% for all procedures. There was no procedure-related mortality. Ketamine administration was not associated with increased complications.Ketamine appears to be a safe anesthetic option for children with PAH. We report rates for cardiopulmonary resuscitation and mortality that are more favorable than those previously reported.
Neurologic injury is a feared and serious long-term complication of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Postoperative hyperthermia was found to enhance postischemic neurologic injury. The use of core temperature as the reference point through CPB assumes parallel changes in brain temperature. We tested the hypothesis that regional and deep brain temperature (DBT) differ during cooling, DHCA, and rewarming.Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature (RT) of 18 degrees C, 30 minutes of DHCA were initiated, and subsequently the piglets were rewarmed to RT of 36.5 degrees C and weaned from CPB. Temperature probes were inserted into the DBT targeting the caudate and thalamic nuclei, their position confirmed by pathology. Superficial brain temperature was measured by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and tympanic (TT) temperatures were recorded.During cooling the deep brain cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT accurately. During rewarming DBT was significantly higher than RT and TT. By the end of rewarming the difference between the deep brain and the RT reached statistical significance (30 minutes: 35.1 +/- 0.7 vs. 32.3 +/- 0.7 p < 0.05, respectively, 40 minutes: 37.5 +/- 0.3 vs. 34.7 +/- 0.8 p < 0.05, respectively).Deep brain hyperthermia routinely occurs during the last stages of rewarming following DHCA. DBT is accurately reflected by NPT and is directly correlated with inflow temperature. Therefore, during rewarming inflow temperatures should not exceed 36 degrees C and NPT should be closely monitored.
Pluripotent cardiac progenitor cells resident in myocardium offer a potentially promising role in promoting recovery from injury. In pediatric congenital heart disease (CHD) patients, manipulation of resident progenitor cells may provide important new approaches to improving outcomes. Our study goals were to identify and quantitate populations of progenitor cells in human neonatal myocardium during the early postnatal period and determine the proliferative capacity of differentiated cardiac myocytes.Immunologic markers of cell lineage (stage-specific embryonic antigen 4 [SSEA-4], islet cell antigen 1 [Isl1], c-kit, Nkx2.5, sarcoplasmic reticulum calcium-regulated ATPase type 2 [SERCA2]) and proliferation (Ki67) were localized in right ventricular biopsies from 32 CHD patients aged 2 to 93 days.Neonatal myocardium contains progenitor cells and transitional cells expressing progenitor and differentiated myocyte marker proteins. Some cells expressed the pluripotent cell marker c-kit and also coexpressed the myocyte marker SERCA2. Multipotent progenitor cells, identified by the expression of Isl1, were found. Ki67 was expressed in some myocytes and in nonmyocyte cells. A few cells expressing SSEA-4 and Isl1 were observed during the early postnatal period. Cells expressing c-kit, the premyocyte marker Nkx2.5, and Ki67 were found throughout the first postnatal month. A progressive decline in cell density during the first postnatal month was observed for c-kit+ cells (p = 0.0013) and Nkx2.5+ cells (p = 0.0001). The percentage of cells expressing Ki67 declined during the first 3 postnatal months (p = 0.0030).Cells in an incomplete state of cardiomyocyte differentiation continue to reside in the infant heart. However, the relative density of progenitor cells declines during the first postnatal month.
Neonates undergoing open-heart surgery are especially at risk for massive bleeding and pronounced inflammation. The efficacy of aprotinin, a serine protease inhibitor, at ameliorating these adverse effects of cardiopulmonary bypass has not been clearly demonstrated in neonates.Term neonates were enrolled and randomly assigned in a blinded fashion to receive saline (group P, placebo) or high-dose aprotinin (group A). Intraoperative management was standardized: surgeon, anesthesia, cardiopulmonary bypass and hemostasis therapy. Patients were admitted postoperatively to a pediatric cardiac intensive care unit. Primary outcome measure of efficacy was duration of the postoperative mechanical ventilation. Secondary outcome measures were total volume and units of blood products transfused intraoperatively and for 24 h after surgery, duration of chest tube in situ, and intensive care and hospital stays after surgery.Twenty-six neonates were enrolled; 13 received aprotinin and 13 received placebo. The study was halted prematurely because of US Food and Drug Administration's concerns about aprotinin's safety. Baseline patient, surgery and cardiopulmonary bypass characteristics were similar between groups. No outcome variables differed between groups (P > 0.05). Duration of postoperative ventilation was 115 +/- 139 h (group A); 126 +/- 82 h (group P); P = 0.29, and total blood product exposure was 8.2 +/- 2.6 U (group A); 8.8 +/- 1.4 U (group P); P = 0.1. Postoperative blood creatinine values did not differ between groups. In-hospital mortality rate was 4%.Aprotinin was not shown to be efficacious in neonates undergoing open-heart surgery. It is unclear whether adult aprotinin safety data are relevant to neonates undergoing open-heart surgery.
The use of ketamine in children with increased pulmonary vascular resistance is controversial. In this prospective, open label study, we evaluated the hemodynamic responses to ketamine in children with pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg).Children aged 3 mo to 18 yr with pulmonary hypertension, who were scheduled for cardiac catheterization with general anesthesia, were studied. Patients were anesthetized with sevoflurane (1 minimum alveolar anesthetic concentration [MAC]) in air while breathing spontaneously via a facemask. After baseline catheterization measurements, sevoflurane was reduced (0.5 MAC) and ketamine (2 mg/kg IV over 5 min) was administered, followed by a ketamine infusion (10 microg x kg(-1) x min(-1)). Catheterization measurements were repeated at 5, 10, and 15 min after completion of ketamine load. Data at various time points were compared (ANOVA, P < 0.05).Fifteen patients (age 147, 108 mo; median, interquartile range) were studied. Diagnoses included idiopathic pulmonary arterial hypertension (5), congenital heart disease (9), and diaphragmatic hernia (1). At baseline, median (interquartile range) baseline pulmonary vascular resistance index was 11.3 (8.2) Wood units; 33% of patients had suprasystemic mean pulmonary artery pressures. Heart rate (99, 94 bpm; P = 0.016) and Pao2 (95, 104 mm Hg; P = 007) changed after ketamine administration (baseline, 15 min after ketamine; P value). There were no significant differences in mean systemic arterial blood pressure, mean pulmonary artery pressure, systemic or pulmonary vascular resistance index, cardiac index, arterial pH, or Paco2.In the presence of sevoflurane, ketamine did not increase pulmonary vascular resistance in spontaneously breathing children with severe pulmonary hypertension.
This report describes a case of thoracoscopic repair of esophageal atresia with a rare type D tracheoesophageal fistula in a child with complex congenital heart disease. We demonstrate the feasibility of thoracoscopic repair and anesthetic management in a child with complex congenital heart disease.
The initial findings from the Pediatric Perioperative Cardiac Arrest (POCA) Registry (1994-1997) revealed that medication-related causes, often cardiovascular depression from halothane, were the most common. Changes in pediatric anesthesia practice may have altered the causes of cardiac arrest in anesthetized children.Nearly 80 North American institutions that provide anesthesia for children voluntarily enrolled in the Pediatric Perioperative Cardiac Arrest Registry. A standardized data form for each perioperative cardiac arrest in children < 0.05). Cardiovascular causes of cardiac arrest were the most common (41% of all arrests), with hypovolemia from blood loss and hyperkalemia from transfusion of stored blood the most common identifiable cardiovascular causes. Among respiratory causes of arrest (27%), airway obstruction from laryngospasm was the most common cause. Vascular injury incurred during placement of central venous catheters was the most common equipment-related cause of arrest. The cause of arrest varied by phase of anesthesia care (P < 0.01). Cardiovascular and respiratory causes occurred most commonly in the surgical and postsurgical phases, respectively.A reduction in the proportion of arrests related to cardiovascular depression due to halothane may be related to the declining use of halothane in pediatric anesthetic practice. The incidence of the most common remaining causes of arrest in each category may be reduced through preventive measures.
Children with cardiomyopathy (CM) often undergo procedures that require general anesthesia (GA) but little is known about anesthesia-related adverse events or postprocedural outcomes.After approval, all children with CM who underwent nonopen heart surgical procedures and/or diagnostic imaging under GA at a tertiary children's hospital during January 2002 to May 2005 were identified from a clinical database. Based on their preprocedure fractional shortening (FS) on echocardiogram, systemic ventricular dysfunction was categorized as mild (FS 23-28%), moderate (FS 16-22%), or severe (FS < 16%) and those with normal (FS > 28%) were excluded from review.Twenty-six patients underwent 34 procedures under GA, of whom 13 (38%) had mild or moderate ventricular dysfunction and 21 (62%) had severe dysfunction. Common procedures included pacer/defibrillator placement (43%) and imaging studies (18%). Eighteen complications were noted in 12 patients. Fifteen (83%) complications occurred in patients with severe ventricular dysfunction. One patient with severe ventricular dysfunction died (3% mortality). Hypotension requiring inotropic support was the most frequent complication (61%). Children with severe ventricular dysfunction often required hospital support pre- and postprocedure with 67% requiring intensive care. Hospital stay was longer for patients with severe ventricular dysfunction compared with children with mild or moderate ventricular dysfunction (P = 0.006).The 30-day mortality rate was low but complications were common, especially in patients with severe ventricular dysfunction. For these patients, we recommend early consideration of perioperative intensive care support to optimize cardiovascular therapy and monitoring.
Laparoscopy has advanced the care of children for a variety of pediatric surgical diseases. However, complication rates for laparoscopic interventions in neonates with hypoplastic left heart syndrome (HLHS) have not been well described. The purpose of this study is to present the largest reported series of laparoscopic surgery performed in patients with HLHS.We conducted a single-institution, retrospective chart review for all neonates with HLHS who underwent a laparoscopic procedure from September 2002 to March 2005. Data regarding patient characteristics, intraoperative monitoring, previous cardiac surgery, perioperative complications, and postoperative mortality were assessed.Twelve patients with HLHS underwent a total of 13 operations during the study period (8 combined Nissen fundoplication and gastrostomy tubes, 3 isolated gastrostomy tubes, 1 Ladd procedure, and 1 combined Nissen fundoplication and gastrocutaneous fistula closure). All cases were completed laparoscopically. Patients had undergone palliative cardiac surgery but were not completely corrected; therefore, they were cyanotic. Perioperative complications were observed in 6 patients (3 gastrostomy tube site infections, 1 small bowel obstruction, 1 postoperative sepsis, and 1 urinary tract infection). There was no mortality in this series.From this experience, it appears that laparoscopy can be performed safely and with satisfactory outcomes in patients with HLHS. However, a multidisciplinary approach, including the availability of a skilled and experienced cardiac anesthesia team, is believed to be critical to optimize outcomes in these critically ill children.
With advances in medical care, survival after cardiac surgery for congenital heart disease has dramatically improved, and attention is increasingly focused on long-term functional morbidities, especially neurodevelopmental outcomes, with their profound consequences to patients and society. There are multiple reasons for concern about brain injury. Some cardiac defects are associated with brain anomalies and altered cerebral blood flow regulation. Brain imaging studies have demonstrated that injury to gray and white matter is quite frequent before heart surgery in neonates. Cardiopulmonary bypass and deep hypothermic circulatory arrest are associated with short- and longer-term adverse neurologic outcome. Additional brain injury can occur during the patient's recovery from surgery. Strategies to optimize neurologic outcome continue to evolve. With new technological developments, perioperative neurologic monitoring of small children has become easier, and data suggest these modalities usefully identify adverse neurologic events and might predict outcome. Monitoring methods to be discussed include processed electroencephalography, near infrared spectroscopy, and transcranial Doppler ultrasound. Alternative perfusion techniques to deep hypothermic circulatory arrest have been developed, such as regional antegrade cerebral perfusion during cardiopulmonary bypass. Other neuroprotective strategies employed during open-heart surgery include temperature regulation, acid-base management, degree of hemodilution, blood glucose control and anti-inflammatory therapies. Evidence of the impact of these measures on neurologic outcome is examined, and deficiencies in our current understanding of neurologic function in children with congenital heart disease are identified.
Regional low-flow perfusion has been used to minimize ischemic brain injury during complex heart surgery in children. However, optimal regional low-flow perfusion remains undetermined. Visible light spectroscopy is a reliable method for continuous determination of capillary oxygen saturation (SgvO2). We used visible light spectroscopy to follow deep and superficial brain SgvO2 during cardiopulmonary bypass, regional low-flow perfusion, and deep hypothermic circulatory arrest.Visible light spectroscopy probes were inserted into the superficial and deep brain of neonatal (3.9-4.5 kg) piglets, targeting the caudate and thalamic nuclei. The piglets were subjected to cardiopulmonary bypass and cooled to a rectal temperature of 18 degrees C using pH stat. Regional low-flow perfusion was initiated through the innominate artery at 18 degrees C, and pump flows were adjusted to 40, 30, 20, and 10 mL/kg/min for 10-minute intervals followed by 30 minutes of deep hypothermic circulatory arrest. Regional low-flow perfusion was reestablished, and flows were increased in a stepwise manner from 10 to 40 mL/kg/min. SgvO2 was continuously monitored. Carotid flow was measured using a flow probe, and cerebral blood flow (milliliters per kilogram body weight per minute) was calculated.There were no significant differences between the deep and superficial brain tissue oxygenation during regional low flow brain perfusion before deep hypothermic circulatory arrest. However, after deep hypothermic circulatory arrest, the superficial brain SgvO2 was lower than the deep brain SgvO2 (24 +/- 12 vs 55.3 +/- 8, P = .05, at flows of 30 mL/kg/min, and 34.2 +/- 17 vs 62.5 + 8, P = .06, at a flow rate of 40 mL/kg/min). During regional low-flow perfusion, SgvO2 was maintained at flows of 30 to 40 mL/kg/min (cerebral blood flows of 15 to 21 mL/kg/min and 19 to 24 mL/kg/min, respectively), but was significantly lower at pump flows of 20 mL/kg/min (cerebral blood flow of 10 to 14 mL/kg/min) and 10 mL/kg/min (cerebral blood flow of 5 to 9 mL/kg/min) compared with the values obtained just before regional low-flow perfusion (pre-deep hypothermic circulatory arrest, 37 +/- 6 vs 65.5 +/- 4.4, P < .05, and 21.6 +/- 3.7 vs 65.5 +/- 4.4, P < .01, respectively; and post-deep hypothermic circulatory arrest, 32 +/- 4.5 vs 65.5 +/- 4.4, P < .05, and 16.6 +/- 4.7 vs 65.5 +/- 4.4, P < .01, respectively).Regional low-flow perfusion at pump flows of 30 to 40 mL/kg/min with resulting cerebral blood flows of 14 to 24 mL/kg/min was adequate in maintaining both deep and superficial brain oxygenation. However, lower pump flows of 20 and 10 mL/kg/min, associated with cerebral blood flow of 9 to 14 mL/kg/min, resulted in significantly reduced SgvO2 values.
This prospective study compared clinical outcomes after heart surgery between three groups of infants with congenital heart disease. One group received dilutional conventional ultrafiltration (group D), another received modified ultrafiltration (group M), and a third group received both dilutional conventional and modified ultrafiltration (group B). We hypothesized that group B patients would have the best clinical outcome.Children younger than 1 year undergoing heart surgery for biventricular repair by the same surgeon were randomly allocated to one of the three study groups. Patient management was standardized, and intensive care staff were blinded to group allocation. Primary outcome measure was duration of postoperative mechanical ventilation. Other outcome measures recorded included total blood products transfused, duration of chest tube in situ, chest tube output, and stays in intensive care and in the hospital.Sixty infants completed study protocol. Mean age and weight were as follows: group D (n = 19), 61 days, 4.3 kg; group M (n = 20), 64 days, 4.5 kg; and group B (n = 21), 86 days, 4.4 kg. Preoperative and intraoperative characteristics were similar between groups. Ultrafiltrate volumes obtained were 196 +/- 93 mL/kg in group D, 105 +/- 33 mL/kg in group M, and 261 +/- 113 mL/kg in group B. There were no significant differences between groups for any outcome variable. Technical difficulties prevented completion of modified ultrafiltration in 2 of 41 infants.There was no clinical advantage in combining conventional and modified ultrafiltration. Because clinical outcomes were similar across groups, relative risks of the ultrafiltration strategies may influence choice.
Daily variability in volume of elective pediatric procedures that require anesthesia may lead to an imbalance between available operating room resources and case load. Longer intervals between scheduling and the surgical date generally result in higher operating room utilization. In this study, we sought to determine which factors influence when parents schedule their children for procedures. We also aimed to identify parents' ideal and longest acceptable waiting intervals and determine whether type of procedure, for example, affects scheduling. From a convenience sample of 250 randomly selected parents of children presenting for elective surgery, 236 completed surveys were analyzed. The remaining 14 surveys were not returned. Overall, parents scheduled their child's procedure a median of 4.3 wk (interquartile range 2.0-8.6) in advance and reported an ideal waiting interval of 3 wk (interquartile range 2-4), and longest acceptable interval of 6 wk (interquartile range 4-10). Parents were willing to wait longer to schedule cardiac (4 wk, P = 0.004) and plastic (3.5 wk, P = 0.024) surgery when compared with general surgical procedures. Overall, parents ranked severity of the child's illness, earliest available time, and surgeon's suggested date as the three most important factors influencing when their child's surgery is scheduled. The timetable for scheduling procedures was highly correlated with both mother and father having available time off work (tau(b) = 0.72, P < 0.0001). Surprisingly, parents did not show a preference for scheduling cases during vacation or summer months.
Visible light spectroscopy (VLS) is newer technology that measures real-time tissue oxygenation. It has been validated in detecting mucosal ischemia in adults. During complex neonatal heart surgery, antegrade cerebral perfusion (ACP) maintains cerebral saturation. Whether ACP maintains peripheral tissue perfusion in humans is not known.Five patients undergoing neonatal open heart surgery with hypothermic cardiopulmonary bypass (CPB) were studied using a VLS esophageal probe in addition to bilateral near infrared cerebral oximetry. Three of five patients required ACP for arch repair, while two patients did not. VLS and cerebral saturation data were collected and analyzed in 5 min intervals prior to CPB, during CPB, and during ACP.In the two patients undergoing heart surgery with routine hypothermic CPB, both cerebral and esophageal saturations were maintained. However in all three neonates requiring ACP, although cerebral saturations did not decrease, esophageal saturation fell below the ischemic threshold (35%). Following establishment of normal CPB, esophageal saturation returned to baseline.Antegrade cerebral perfusion maintains cerebral oxygen delivery, however, it does not adequately perfuse the esophagus in neonates. This could have clinical implications.
To observe the effects of right carotid artery ligation and variations in extracorporeal life support (ECLS) flow on regional cerebral oxygenation index (rSO2i) measured using near infrared spectroscopy.Prospective observational study.Tertiary children's hospital.Eleven neonatal and pediatric patients requiring veno-arterial ECLS support between June 2000 and March 2003.Near infrared spectroscopy probe placement on left and right frontal regions of patients undergoing ECLS, before vessel cannulation or within 24 hrs of initiation of ECLS.Regional cerebral oxygenation was measured every minute for 72 hrs or until the patient was decannulated. The effect of cannulation on rSO2i from each hemisphere of the brain and the relationship between ECLS flow and rSO2i during ECLS support and "trialing off" periods were determined. Ligation of the right carotid artery resulted in a 12-25% decrease in rSO2i from baseline in the right frontal region for a duration ranging from 17 to 45 mins before returning toward baseline. No substantial change in the left frontal region rSO2i was detected during cannulation. Following this depression in rSO2i on the right, there was a transient increase above baseline in rSO2i observed in both hemispheres on initiating ECLS. No correlation between ECLS flow and rSO2i was found over the 72-hr period. Periods of "trialing off" ECLS were not related to any change in rSO2i in either hemisphere.This study demonstrated no relationship between ECLS flow and rSO2i changes during the 72-hr observation period. A brief period of cerebral oxygen desaturation of the right frontal region at the time of right carotid ligation was seen in all three study patients examined during cannulation, followed by an increased rSO2i with initiation of ECLS flow. Near infrared spectroscopy measurement may offer an important adjunct for neurologic monitoring of ECLS patients.
Anesthesia considerations for pediatric thoracic solid organ transplant. Anesthesiology clinics of North America Williams, G. D., Ramamoorthy, C. 2005; 23 (4): 709-?
This article discusses the indications, perioperative management, postoperative complications, and patient outcome of pediatric heart transplantation and pediatric lung transplantation. Special emphasis is placed on the anesthetic considerations relevant for children who are undergoing or have received a solid thoracic organ transplant.
Deep hypothermic circulatory arrest (DHCA) has been used for the past 50 years in the surgical repair of complex congenital cardiac malformations and operations involving the aortic arch; it enables the surgeon to achieve precise anatomical reconstructions by creating a bloodless operative field. Nevertheless, DHCA has been associated with immediate and late neurodevelopmental morbidities. This review provides an overview of the pathophysiology of neonatal hypoxic brain injury after DHCA, focusing on cellular mechanisms of necrosis, apoptosis, and glutamate excitotoxicity. Techniques and strategies in neonatal brain protection include hypothermia, acid base blood gas management during cooling, and pharmacologic interventions such as the use of volatile anesthetics. Surgical techniques consist of intermittent cerebral perfusion during periods of circulatory arrest and continuous regional brain perfusion.
Estimating appropriate tracheal tube (TT) depth following tracheal intubation in infants and children presents a challenge to anesthesia practitioners. We evaluated three methods commonly used by anesthesiologists to determine which one most reliably results in appropriate positioning.After IRB approval, 60 infants and children scheduled for fluoroscopic procedures requiring general anesthesia were enrolled. Patients were randomly assigned to one of three groups: (1) deliberate mainstem intubation with subsequent withdrawal of the TT 2 cm above the carina ('mainstem' method); (2) alignment of the double black line marker near the TT tip at the vocal cords ('marker' method); or (3) placement of the TT at a depth determined by the formula: TT depth (cm) = 3 x TT size (mmID) ('formula' method). TT tip position was determined to be 'appropriate' if located between the sternoclavicular junction (SCJ) and 0.5 cm above the carina as determined by fluoroscopy. Risk ratios were calculated, and data were analysed by the chi-square test accepting statistical significance at P < 0.05.The mainstem method was associated with the highest rate of appropriate TT placement (73%) compared with both the marker method (53%, P = 0.03, RR = 1.56) and the formula method (42%, P = 0.006, RR = 2.016). There was no difference between the marker and formula methods overall (P = 0.2, RR = 1.27). Analysis of age-stratified data demonstrated higher success with the marker method compared with the formula method for patients 3-12 months (P = 0.0056, RR = 4.0).Deliberate mainstem intubation most reliably results in appropriate TT depth in infants and children.
A neonate with VACTERL association including tricuspid atresia was scheduled for thoracoscopic esophageal atresia with tracheoesophageal fistula (EA/TEF) repair and laparoscopic gastrostomy tube placement. In addition to standard noninvasive monitoring, arterial blood pressure, central venous pressure, and cerebral oxygen saturation were monitored. Gastric distension resulting from positive pressure ventilation prevented laparoscopic gastrostomy tube placement. Thoracoscopy with a CO2 insufflation pressure of 6 mm Hg at low flow (1 L/min) was well tolerated hemodynamically despite hypercarbia and cerebral oxygen saturation was maintained. Careful monitoring and good communication were critical to the safe management of this single ventricle patient during thoracoscopic EA/TEF repair.Esophageal and tracheoesophageal fistula in conjunction with single ventricle physiology carries a significant risk of mortality. We present the anesthetic management of a neonate with unpalliated tricuspid atresia who underwent thoracoscopic tracheoesophageal fistula repair.
The safety of laparoscopic surgery in infants with single ventricle physiology has been a subject of controversy despite potential benefits over open surgery. We present the anesthetic management of five infants with palliated hypoplastic left heart syndrome that underwent laparoscopic Nissen fundoplication. After anesthetic induction and tracheal intubation, an intraarterial catheter was placed for hemodynamic monitoring. Insufflation pressure was limited to 12 mm Hg and was well tolerated by all patients. There were no intraoperative or postoperative complications. In patients with hypoplastic left heart syndrome, laparoscopic Nissen fundoplication can be safely performed with careful patient selection and close intraoperative monitoring.
Fetal cardiac surgery has potential benefits for treatment of some congenital heart defects. However, placental dysfunction as a result of fetal bypass, fetal stress, and fetal exposure to external milieu needs to be overcome to optimize the outcomes of fetal cardiac bypass. In this study we evaluated the technical feasibility of cardiac bypass in the nonhuman primate fetus and the efficacy of different anesthetic approaches.Twelve baboon fetuses, average gestation 146 +/- 8 days and weight 696 +/- 184 g, were used. Three fetuses were excluded from the study because of nuchal cord presentations. The animals were separated into two anesthesia groups: isoflurane (n = 6) and fentanyl and midazolam (n = 3). A miniature roller pump circuit without oxygenator was used for fetal bypass for 30 minutes. No blood transfusion was performed. Fetal blood gas samples were collected before bypass, during bypass, and at 15 and 60 minutes after bypass.All fetuses in the isoflurane group were successfully placed on the cardiac bypass circuit. However, 2 animals in the fentanyl and midazolam group were not placed on the bypass circuit because of sustained elevation in maternal uterine tone. All maternal baboons survived. Of the 6 fetuses in the isoflurane group, 5 survived for 60 minutes; however, placental function continued to deteriorate after bypass (Pa o 2 33 +/- 3 mm Hg before bypass, 23 +/- 6 mm Hg 15 minutes after, and 18 +/- 9 mm Hg 60 minutes after).The technical feasibility of cardiac bypass in nonhuman primate fetuses weighing less than 1000 g was confirmed. Isoflurane anesthesia appears to be superior to fentanyl and midazolam anesthesia for fetal cardiac surgery because of adequate uterine relaxation.
The incidence of neurological complications after pediatric cardiac surgery ranges from 2% to 25%. The causes are multifactorial and include preoperative brain malformations, perioperative hypoxemia and low cardiac output states, sequelae of cardiopulmonary bypass, and deep hypothermic circulatory arrest. Neurological monitoring devices are readily available and the anesthesiologist can now monitor the brain during pediatric cardiac surgery. In this review we discuss near-infrared cerebral oximetry, transcranial Doppler ultrasound, and electroencephalographic monitors for use during congenital heart surgery. After review of the basic principles of each monitoring modality, we discuss their uses during pediatric heart surgery. We present evidence that multimodal neurological monitoring in conjunction with a treatment algorithm may improve neurological outcome for patients undergoing congenital heart surgery and present one such algorithm.
Deep hypothermic circulatory arrest (DHCA), as used in infant heart surgery, carries a risk of brain injury. In a piglet DHCA model, neocortical neurons appear to undergo apoptotic death. Caspases, cytochrome c, tumor necrosis factor (TNF), and Fas play a role in apoptosis in many ischemic models. This study examined the expression of these factors in a DHCA piglet model.Thirty-nine anesthetized piglets were studied. After cardiopulmonary bypass (CPB) cooling of the brain temperature to 19 degrees C, DHCA was induced for 90 min, followed by CPB rewarming. After separation from CPB, piglets were killed at 1, 4, 8, 24, and 72 h and 1 week. Caspase-8 and -3 activity, and concentrations of TNF-alpha, Fas, Fas-ligand, cytochrome c, and adenosine triphosphate (ATP) were measured in the neocortex by enzymatic assay and Western blot analysis. Caspase-8 and -3 activity and cell death were examined histologically. Significance was set at P < 0.05.In neocortex, damaged neurons were not observed in control (no CPB), rarely observed in CPB (no DHCA), and rarely observed in the DHCA 1-h, 4-h, and 1-week reperfusion groups. However, they were seen frequently in the DHCA 8-, 24-, and 72-h reperfusion groups. Although neuronal death was widespread 8-72 h after DHCA, cortical ATP concentrations remained unchanged from control. Both caspase-3 and -8 activities were significantly increased at 8 h after DHCA, and caspase-3 concentration remained elevated for as long as 72 h. Caspase-3 and -8 activity was also observed in damaged neocortical neurons. Cytosolic cytochrome c and Fas were significantly expressed at 1 h and 4 h after DHCA, respectively. Fas-ligand and TNF-alpha were not observed in any group.After DHCA, induction of apoptosis in the neocortex occurs within a few hours of reperfusion and continues for several days. Increased Fas, cytochrome c, and caspase concentrations, coupled with normal brain ATP concentrations and apoptotic histologic appearance, are consistent with the occurrence of apoptotic cell death.
Relatively rare adverse events, such as unexpected cardiac arrest, are difficult to study in the clinical setting. These events are often unpredictable in their occurrence (prompting interest in their investigation) and do not occur with sufficient frequency in any single institution to provide an adequate sample for analysis. A disease-specific registry is an epidemiological technique that can be used to collect data on a set of relatively rare unpredictable events. This approach was adopted for investigation of cardiac arrest in children when it became apparent from analysis of malpractice claims that a significant clinical problem existed. This report provides a brief historical account of the development of the Pediatric Peri-Operative Cardiac Arrest (POCA) Registry and elaborates on the methodology including strengths, weaknesses, and practical implementation issues.
Neonates with functional single ventricle often require hypoxic or hypercapnic inspired gas mixtures to reduce pulmonary overcirculation and improve systemic perfusion. Although the impact of these treatments on arterial oxygen saturation has been described, the effects on cerebral oxygenation remain uncertain. This study examined the effect of these treatments on cerebral oxygen saturation and systemic hemodynamics.Neonates with single ventricle mechanically ventilated with room air were enrolled in a randomized crossover trial of 17% inspired oxygen or 3% inspired carbon dioxide. Each treatment lasted 10 min, followed by a 10-20-min washout period. Cerebral and arterial oxygen saturation were measured by cerebral and pulse oximetry, respectively. Cerebral oxygen saturation, arterial oxygen saturation, and other physiologic data were continuously recorded.Three percent inspired carbon dioxide increased cerebral oxygen saturation (56 +/- 13 to 68 +/- 13%; P < 0.01), whereas 17% inspired oxygen had no effect (53 +/- 13 to 53 +/- 14%; P = 0.8). Three percent inspired carbon dioxide increased the mean arterial pressure (45 +/- 8 to 50 +/- 9 mmHg; P < 0.01), whereas 17% inspired oxygen had no effect. And 3% inspired carbon dioxide decreased arterial pH and increased arterial carbon dioxide and oxygen tensions.Inspired 3% carbon dioxide improved cerebral oxygenation and mean arterial pressure. Treatment with 17% inspired oxygen had no effect on either.
Several techniques have been suggested to reduce the trauma of nasotracheal intubation, although no comparative studies exist. The authors evaluated red-rubber catheters as a guide to nasotracheal intubation.Children presenting for elective surgery were randomized to undergo red-rubber catheter-guided nasotracheal intubation or to have the nasotracheal tube alone inserted. After general anesthesia and paralysis with vecuronium, the nares were prepared with topical vasoconstrictor. The nasotracheal tube was softened with warm water. In the catheter-guided group, the nasotracheal tube tip was fitted to the trailing end of the red-rubber catheter, and the two were advanced together. The red-rubber catheter was retrieved from the nasopharynx, disconnected, and removed. In the other group, the nasotracheal tube was advanced blindly into the nasopharynx. In both groups, intubation was then completed during direct laryngoscopy using Magill forceps. A blinded observer swabbed the pharynx and rated the severity of bleeding based on reference photographs.Age, weight, snoring history, and difficulty of intubation were not different between groups. Obvious bleeding was lower using the red-rubber catheter technique (10 vs. 29%, P = 0.013), which took longer to perform (74 vs. 56 s, P = 0.02).Although the incidence of bleeding in both groups was similar, severity of bleeding was reduced in the catheter-guided group during nasotracheal intubation. Use of a red-rubber catheter may reduce the trauma associated with nasotracheal intubation.
Management strategies for preoperative infants with hypoplastic left heart syndrome (HLHS) include increased inspired nitrogen (hypoxia) and increased inspired carbon dioxide (hypercarbia). There are no studies directly comparing these 2 therapies in humans. This study compares the impact of hypoxia versus hypercarbia on oxygen delivery, under conditions of fixed minute ventilation.Ten anesthetized and paralyzed preoperative infants with HLHS were evaluated in a prospective, randomized, crossover trial comparing hypoxia (17% FIO(2)) with hypercarbia (2.7% FICO(2)). Each patient was treated in a random order (10 minutes per condition) with a recovery period (15 to 20 minutes) in room air. Arterial (SaO(2)) and superior vena caval (SvO(2)) co-oximetry and cerebral oxygen saturation (ScO(2)) measurements were made at the end of each condition and recovery period. ScO(2) was measured by near infrared spectroscopy. Hypoxia significantly decreased both SaO(2) (-5.2+/-1.1%, P=0.0014) and SvO(2) (-5.6+/-1.7%, P=0.009) compared with baseline, but arteriovenous oxygen saturation (AVO(2)) difference (SaO(2)-SvO(2)) and ScO(2) remained unchanged. Hypercarbia decreased SaO(2) (-2.6+/-0.6%, P=0.002) compared with baseline but increased both ScO(2) (9.6+/-1.8%, P=0.0001) and SvO(2) (6+/-2.2%, P=0.022) and narrowed the AVO(2) difference (-8.5+/-2.3%, P=0.005). Both hypoxia and hypercarbia decreased the balance between pulmonary and systemic blood flow (Qp:Qs) compared with baseline.In preoperative infants with HLHS, under conditions of anesthesia and paralysis, although Qp:Qs falls in both conditions, oxygen delivery is unchanged during hypoxia and increased during hypercarbia. These data cannot differentiate cerebral from systemic oxygen delivery.
The Pediatric Perioperative Cardiac Arrest (POCA) Registry was formed in 1994 in an attempt to determine the clinical factors and outcomes associated with cardiac arrest in anesthetized children.Institutions that provide anesthesia for children are voluntarily enrolled in the POCA Registry. A representative from each institution provides annual institutional demographic information and submits anonymously a standardized data form for each cardiac arrest (defined as the need for chest compressions or as death) in anesthetized children 18 yr of age or younger. Causes and factors associated with cardiac arrest are analyzed.In the first 4 yr of the POCA Registry, 63 institutions enrolled and submitted 289 cases of cardiac arrest. Of these, 150 arrests were judged to be related to anesthesia. Cardiac arrest related to anesthesia had an incidence of 1.4 +/- 0.45 (mean +/- SD) per 10,000 instances of anesthesia and a mortality rate of 26%. Medication-related (37%) and cardiovascular (32%) causes of cardiac arrest were most common, together accounting for 69% of all arrests. Cardiovascular depression from halothane, alone or in combination with other drugs, was responsible for two thirds of all medication-related arrests. Thirty-three percent of the patients were American Society of Anesthesiologists physical status 1-2; in this group, 64% of arrests were medication-related, compared with 23% in American Society of Anesthesiologists physical status 3-5 patients (P < 0.01). Infants younger than 1 yr of age accounted for 55% of all anesthesia-related arrests. Multivariate analysis demonstrated two predictors of mortality: American Society of Anesthesiologists physical status 3-5 (odds ratio, 12.99; 95% confidence interval, 2.9-57.7), and emergency status (odds ratio, 3. 88; 95% confidence interval, 1.6-9.6).Anesthesia-related cardiac arrest occurred most often in patients younger than 1 yr of age and in patients with severe underlying disease. Patients in the latter group, as well as patients having emergency surgery, were most likely to have a fatal outcome. The identification of medication-related problems as the most frequent cause of anesthesia-related cardiac arrest has important implications for preventive strategies.
We sought to examine the effects of modified venovenous ultrafiltration after cardiopulmonary bypass on pulmonary compliance in infants.We prospectively enrolled 38 infants undergoing their first operation for congenital heart disease. Infants were randomized to receive 20 minutes of modified ultrafiltration after bypass or control. Static and dynamic compliance was measured after induction of anesthesia, before and immediately after filtration in the operating theater, 1 hour after return to the pediatric intensive care unit, and 24 hours after the operation. Length of time on the ventilator, inotropic requirements, and length of stay in the intensive care unit were recorded.Modified ultrafiltration produced a significant immediate improvement in dynamic (pre-ultrafiltration 2.5 +/- 1.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.7 mL/cm H(2)O, P =.03) and static (pre-ultrafiltration 2.1 +/- 0.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.1 mL/cm H(2)O, P =.04) compliance. However, there was no significant difference in the change in dynamic (P =.3) or static (P =.7) compliance in the ultrafiltration and control groups when compared before the operation, after the operation, and at 24 hours. There was no significant difference in the time to extubation between patients and control subjects (140 +/- 91 hours vs 90 +/- 58 hours) or the length of intensive care unit stay (10.0 +/- 9.1 days vs 7.4 +/- 5.7 days).Modified ultrafiltration produces an improvement in pulmonary compliance after bypass in infants. However, these improvements are not sustained past the immediate post-ultrafiltration period and do not lead to a decreased length of intubation or intensive care unit stay.
To examine whether coagulation tests, sampled before and during cardiopulmonary bypass (CPB), are related to blood loss and blood product transfusion requirements, and to determine what test value(s) provide the best sensitivity and specificity for prediction of excessive hemorrhage.Prospective.University-affiliated, pediatric medical center.Four hundred ninety-four children.Coagulation tests.Demographic, coagulation test, blood loss, and transfusion data were noted in consecutive children undergoing cardiac surgery. Laboratory tests included hematocrit (Hct), prothrombin time, partial thromboplastin time (PTT), platelet count, fibrinogen concentration, and thromboelastography. Stepwise linear regression analysis indicated that platelet count during CPB was the variable most significantly associated with intraoperative blood loss (in milliliters per kilogram) and 12-hour chest tube output (in milliliters per kilogram). Other independent variables associated with blood loss were thromboelastography maximum amplitude (MA) during CPB, preoperative PTT, preoperative Hct, and preoperative thromboelastography angle and shear modulus values. Thromboelastography MA during CPB was the only variable associated with total products transfused (in milliliters per kilogram). Of all tests studied, platelet count during CPB (< or = 108,000/microL) provided the maximum sensitivity (83%) and specificity (58%) for prediction of excessive blood loss (receiver operating characteristic analysis). Blood loss was inversely related to patient age; neonates received the most donor units (median, 8 units; range, 6 to 10 units).During cardiac surgery, coagulation tests (including thromboelastography) drawn pre-CPB and during CPB are useful to identify children at risk for excessive bleeding. Platelet count during CPB was the variable most significantly associated with blood loss.
In this prospective cohort study of 548 children undergoing open-heart surgery, we evaluated demographic and perioperative factors to identify variables associated with perioperative blood loss and blood product transfusions. Using multivariate analysis, younger patient age was found to be the variable most significantly associated with bleeding and transfusions. Higher preoperative hematocrit, complex surgery, lower platelet count during cardiopulmonary bypass (CPB), and longer duration of deep hypothermic circulatory arrest were also significantly associated with bleeding and transfusion. Excessive postoperative chest tube (CT) drainage was associated with intraoperative bleeding. Independently associated variables accounted for 76% of the variability in CT output measured after 2 h in intensive care. Patients were subdivided into children aged < or =1 yr (infants) and children >1 yr; infants bled more intraoperatively (P<0.005); had greater cumulative CT output at 2, 6, 12, and 24 h (P<0.0001); and received more blood products (P<0.0001). Factors associated with bleeding and transfusions varied with patient age. Lower body core temperature during CPB was highly associated with blood loss and transfusions in infants, whereas resternotomy, preoperative congestive heart failure, and prolonged duration of CPB were significant factors associated with bleeding and transfusions in children >1 yr old.Knowledge of the factors associated with blood loss and blood product transfusions can help to identify children at risk of excessive bleeding after open-heart surgery.
To compare coagulation test results, blood loss, and blood product transfusions between patients receiving prophylactic epsilon-aminocaproic acid (EACA) and a control group matched for age, resternotomy, and surgery in children undergoing cardiac surgery.Nested case-control study.University-affiliated, pediatric medical center.Same study period; 70 patients in EACA group and 70 patients in control group.Prophylactic EACA administered intravenously (load, 150 mg/kg, infusion; 30 mg/kg/h) to 70 patients at increased risk for bleeding (reoperation or Ross procedure).Coagulation test values were measured before, during, and after cardiopulmonary bypass (CPB). Intraoperative blood loss, postoperative chest tube output, and allogenic blood product transfusions were recorded. Comparison of demographic and surgical data indicated close matching of the EACA and control groups. The EACA group ([median, 25th to 75th quartile] 15.6 mL/kg; 9.2 to 26.3 mL/kg) had less intraoperative blood loss than the control group (22.2 mL/kg; 14.3 to 36.3 mL/kg; p = 0.02). Postoperative chest tube output at 6 hours (p = 0.08), 12 hours (p = 0.07), and 24 hours (p = 0.08) was not significantly different between groups. Fewer EACA group patients required reexploration for bleeding (p < 0.05). There was no difference between groups in blood products transfused (in milliliters per kilogram or allogenic exposure per patient). Thromboelastography values (maximum amplitude [MA], whole blood clot lysis index at 30 minutes after MA) during CPB were better preserved in the EACA group.EACA reduced intraoperative blood loss but did not significantly decrease blood product transfusions. Lack of efficacy may be related to relative underdosing and should be further studied.
Thromboelastographic evaluation of the influence of fibrinolysis on blood loss and blood product transfusions in children during cardiac surgery.Prospective study.University-affiliated, pediatric medical center.Two hundred seventy-eight consecutive children undergoing cardiac surgery.Blood sampling for coagulation tests, including native and protamine-modified thromboelastography.Blood coagulation tests were measured before, during, and after cardiopulmonary bypass (CPB). Demographic data, perioperative blood loss, and blood product transfusions were prospectively recorded. Fibrinolysis was defined as thromboelastography of A30/MA less than 0.85 (MA, maximum amplitude; A30, amplitude 30 minutes after MA) and was noted in 3% of children pre-CPB, 16% during CPB, and 3% post-CPB. Fibrinolysis before CPB was associated with poor cardiac output. Fibrinolysis during CPB occurred in young children (aged 350 +/- 836 days) undergoing complex surgery with prolonged CPB (119 +/- 48.8 minutes) and deep hypothermia (25.6 degrees C +/- 4.7 degrees C). These patients received blood products after CPB and were not fibrinolytic after transfusion. They incurred similar blood loss (in mL/kg) and received similar volumes of blood products (mL/kg) as age-matched and surgery-matched patients without fibrinolysis.A group of children at risk for fibrinolysis during CPB was identified. However, fibrinolysis during CPB did not influence blood loss or the total volume of blood products transfused.
To determine if vein localization with an audio Doppler increases successful central venous cannulation and decreases complications in infants and children when performed by inexperienced operators, compared with vein localization by anatomic landmarks (ALs).A prospective cohort of infants and children undergoing central venous cannulation for cardiac surgery.A university-affiliated children's hospital with a pediatric anesthesia fellowship program.All infants and children undergoing cardiac surgery between July 1, 1996, and January 1, 1997.Subjects had central venous catheters (CVCs) placed by an anesthesia fellow by either ALs or audio-Doppler localization of the veins.Eighty-four children were studied. Internal jugular vein (IJV) cannulation was attempted in 71 (85%) children and femoral vein cannulation in 13 (15%) children. Time to catheter insertion, number of needle passes, and artery puncture were noted. Sixty-one of 63 (97%) children had successful central venous cannulation by an anesthesia fellow using audio-Doppler vein localization. This was significantly greater than the 13 of 21 (62%) successful cannulations among children who had veins localized by ALs. Time to insertion did not differ by method of vein localization; however, the number of needle passes was significantly greater in the AL group. Artery puncture did not differ significantly by method of vein localization.Vein localization by audio Doppler significantly increases the rate of successful central venous cannulation and decreases the number of needle passes in pediatric patients when used by inexperienced operators.
Although recent studies indicated young children are at risk for increased perioperative hemorrhage after open heart operations, the associations between patient age, blood loss and blood product transfusions have not been fully defined in children.Perioperative blood loss and blood product transfusion data were recorded for 414 consecutive children undergoing open heart procedures. The children were in the following age groups: 1 month or younger, group 1; older than 1 month to 12 months, group 2; older than 1 year to 5 years, group 3; and older than 5 years, group 4.Postoperative blood loss and blood product transfusions were inversely related to age and differed significantly between the four age groups. Multiple preoperative and intraoperative factors that possibly influence hemostasis also differed significantly between age groups. Median units transfused within 72 hours differed significantly with age (p < 0.0001): group 1, 8 units (range, 1 to 19 units); group 2, 6 units (range, 0 to 21 units); group 3, 2 units (range, 0 to 23 units); and group 4, 0 units (range, 0 to 38 units).Blood loss and transfusions vary inversely with age. Per kilogram of body weight, neonates bled more and received more donor products than any other age group.
Peripherally inserted central venous catheters (PICCs) are commonly used intravenous access devices in children. Although PICCs are intended to be placed in central veins, many fail to reach this location. These noncentral PICCs are used for administration of medications and isotonic solutions.To examine the efficacy of noncentral PICCs for completion of therapy, the complications associated with their use, and the effectiveness of noncentral PICCs as compared with PICCs placed in a central vein.A prospective cohort study of children in whom PICCs were inserted, from January 1, 1994, to January 1, 1996.A university-affiliated teaching institution.Completion of intravenous therapy.A total of 587 PICCs were studied. Thirty-nine percent of PICCs were placed in noncentral veins. Centrally placed PICCs had significantly longer catheter duration compared with those placed noncentrally (16.6 vs 11.4 days, respectively). However, central and noncentral PICCs had similar therapy completion rates (73% and 69%, respectively). Catheter failure because of occlusion and accidental dislodgment were similar for central and noncentral PICCs. Likewise, complications caused by exit-site infection, phlebitis, and catheter-associated sepsis were also similar for catheters in the 2 locations. Catheter survival curves were similar for central and noncentral PICCs.Our study demonstrates that PICCs placed in noncentral veins provide reliable and safe intravenous access for administration of many medications and isotonic solutions for about 2 weeks' duration. The placement of PICCs in central veins may be restricted to those children who need central vascular access because of the type of intended therapy.
This prospective cohort study determined the incidence and risk factors for development of postdural puncture headache (PDPH) in children after lumbar puncture (LP). Eighty-six children were enrolled. LPs were performed with use of 22-gauge spinal needles with the bevel oriented parallel to the long axis of the spine. Follow-up telephone interviews and patients' diary of symptoms were collected. Headache brought on by sitting up and relieved by lying down was defined as PDPH. Of the 80 who completed the study, six (8%) developed PDPH. Two (3%) were less than 6 years old and four (5%) were 6 to 12 years of age. Children with a history of headache following a previous LP were nine times as likely to experience PDPH. PDPH occurs not infrequently in children. A prior history of headache is a predisposing factor.
Injury associated with ischemia and reperfusion is a significant factor in a number of clinical diseases. We have completed a number of preclinical studies investigating the blockade of leukocyte adhesion molecules in ischemia-reperfusion injury. In our work and in the work of other investigators, monoclonal antibodies directed to CD18, P-selectin and L-selectin were effective in reducing ischemia-reperfusion injury to the rabbit ear and in reducing injury following hemorrhagic shock in both rabbits and nonhuman primates. Ischemia-reperfusion injury was also reduced by synthetic oligosaccharide sLe(x). These studies suggest that adhesion blockade might be effective in the clinical setting.
We investigated the pharmacokinetics and side effects of milrinone in infants and children (< or = 13 yr) after open heart surgery in this prospective, open-label study. Milrinone binding to cardiopulmonary bypass (CPB) circuitry was also examined in out two groups. Children in the small dose group (n = 11) received two 25-microg/kg boluses with a final infusion rate of 0.5 microg kg(-1) x min(-1); those in the large dose group (n = 8) received a 50-microg/kg bolus and a 25-microg/kg bolus with a final infusion rate of 0.75 microg x kg(-1) x min(-1). Blood samples for milrinone concentration were drawn 30 min after each bolus, at steady state, and after discontinuing the milrinone infusion. Pharmacokinetics were evaluated using traditional and nonlinear mixed effects modeling analysis. Milrinone kinetics best fit a two-compartment model. Steady-state plasma levels in the small and large dose groups were within the adult therapeutic range (113 +/- 39 and 206 +/- 74 ng/mL, respectively). The volumes of distribution (Vbeta) in infants (0.9 L/kg) and children (0.7 L/kg) were not different, but infants had significantly lower milrinone clearance (3.8 vs 5.9 mL x kg(-1) x min(-1)). Thrombocytopenia (defined as platelet count < or = 100,000 mm(-3)) occurred in 58%, and the risk increased significantly with duration of infusion. Tachyarrythmias were noted in two patients. Milrinone did not bind to CPB circuitry. We conclude that milrinone is cleared more rapidly in children than in adults. The major complication was thrombocytopenia. Implications: Most pediatric dosing is based on data published for adults. Infants and children have kinetics that differ from adults. We studied the distribution of I.V. milrinone in infants and children after open heart surgery. Milrinone had a larger volume of distribution and a faster clearance in infants and children than in adults, and dosing should be adjusted accordingly.
To determine the effects of red cell separation and ultrafiltration on heparin concentration.Prospective study.University-affiliated, pediatric medical center.Thirty-one children undergoing cardiac surgery.Blood sampled for heparin concentration and coagulation tests.Thirteen infants under-went modified veno-venous ultrafiltration (UF) after cardiopulmonary bypass (CPB). In addition, residual blood in the CPB circuit was hemoconcentrated by UF and reinfused (UF group). Heparin concentration increased from 2.0 +/- 0.6 to 2.5 +/- 0.8 U/mL, following modified UF; while activated coagulation time (ACT) decreased from 701 +/- 177 to 627 +/- 107 seconds. Heparin concentration of CPB circuit residual increased from 1.9 +/- 0.7 to 3.1 +/- 1.0 U/mL. In 18 children (older than 1 year old), the residual blood in the CPB circuit was hemoconcentrated by cell separation (CS) and reinfused (CS group). Heparin concentration of CPB circuit residual decreased from 2.6 +/- 0.6 to 0.3 +/- 0.2 U/mL. After reinfusion, patient heparin concentration remained unchanged at < 0.05 U/mL. Thrombin time increased from 28 +/- 6 to 48 +/- 29 seconds and did not correlate with H.The plasma concentration of heparin increased after veno-venous modified UF of the patient. Heparin concentration also increased after UF of residual CPB circuit blood. In contrast, circuit blood hemoconcentrated by CS contained minimal heparin, and, when infused, did not increase patient's heparin concentration. ACT and thrombin time did not correlate with heparin concentration.
Leukocyte emigration in the lung occurs by both CD18-dependent and -independent mechanisms that are stimulus specific. We examined the effect of CD18 blockade (mAb 60.3) on neutrophil (PMN) emigration into, and bacterial clearance from, the lung. After intravenous treatment with either mAb 60.3 or saline, rabbits were given an intralobar inoculation with 10(9) colony-forming units of either Staphylococcus aureus or Escherichia coli. Four hours after inoculation, lungs were lavaged to assess PMN emigration. CD18 blockade reduced PMN emigration to E. coli by 76% but only 45% to S. aureus. Experiments to determine bacterial recovery from the lungs at 4, 8, and 24 h after inoculation showed that CD18 blockade impaired the early (4 h) clearance of E. coli but not S. aureus. These findings suggest that PMN emigration to intrapulmonary S. aureus is largely CD18-independent. In contrast, intrapulmonary E. coli elicits CD18-mediated PMN emigration. CD18 blockade results in impaired clearance of E. coli but not S. aureus from the lung.
Survey of the use of peripherally inserted central venous catheters in children. Pediatrics Thiagarajan, R. R., Ramamoorthy, C., Gettmann, T., Bratton, S. L. 1997; 99 (2): E4-?
Use of peripherally inserted central venous catheters (PICCs) to provide prolonged intravenous (IV) access in children is increasing. Our goal was to describe the children treated with PICCs in our institution, and to study catheter features such as catheter life, completion of therapy, and complications. Furthermore, we also evaluated PICC use in children completing therapy after discharge from our institution.A prospective study of all PICCs inserted at the Children's Hospital and Medical Center (CHMC), a university-affiliated teaching institution, during a period of 18 months (January 1994 to July 1995).A total of 441 PICCs were inserted in 390 patients. Patient age ranged from 0 to 22 years with a mean of 5.4 +/- 6.0 years. No insertion complications occurred. Treatment of infectious disease (46%) was the most frequent reason for PICC insertion. All pediatric medical and surgical services used PICCs. Average catheter life was 13 +/- 12 days. Sixty-one percent of PICCs were used entirely at CHMC, while 39% were also used at home or at an outside hospital. Completion of therapy was achieved in 69% of PICCs. Among children who completed therapy outside our hospital, there was no difference in the rates of occlusion, accidental dislodgment, or infection. One hundred twenty-nine (29%) PICCs were removed for complications. Occlusion (7%), accidental displacement (8%), and suspicion of sepsis (8%) were the most common complications. Only 2% of PICCs had documented catheter-associated sepsis.PICCs provide reliable and safe access for prolonged IV therapy in neonates and children. The low incidence of complications with PICCs make them an attractive device for prolonged IV access. Similar complication rates with use in and out of hospital suggest that home IV therapy can be safely delivered with PICCs, avoiding expensive hospitalization.
Human newborns, particularly those born before full term, are more susceptible to bacterial infections as a result of impaired host defense mechanisms. Compared with adults, circulating leukocytes from human newborns (preterm and full-term gestations) and newborn rabbits (full-term gestation) have low resting levels of CD62L (L-selectin) and do not significantly increase surface expression of CD18 after inflammatory stimulation. To determine the potential utility of preterm rabbits in investigations of perinatal human conditions, the authors compared the surface expression of the beta 2-integrin CD18 and CD62L (L-selectin) on polymorphonuclear leukocytes (PMNs) from perinatal rabbits and perinatal humans, both under resting conditions and after in vitro activation with inflammatory stimulants.After erythrocyte lysis of whole-blood samples, leukocytes from 7-day-old, full-term (31-day gestation), and preterm (24-day gestation) rabbits, as well as full-term (37-42 week gestation) and preterm (27-36 week gestation) human newborns were prepared and stimulated in vitro at 37 degrees C with either C5a or phorbol myristate acetate. After fluorescence labeling of CD18 and CD62L with monoclonal antibodies, PMN adhesion molecule expression was assessed by flow cytometry.Constitutive CD18 expression was not significantly different between perinatal and adult humans but was reduced in all perinatal rabbits compared with adults. Inflammatory stimulation caused significant increases in CD18 expression in adult human PMNs but not in full-term and preterm newborns. Changes in CD18 expression in adult and preterm rabbits after stimulation, although in the same direction as humans, were more variable. In both species, constitutive CD62L expression on PMNs from all perinates was significantly lower than in adults. However, CD62L was shed to similar degrees after inflammatory stimulation in all groups.Preterm rabbits may provide a potentially useful experimental model to study PMN adhesion and host defense in the perinatal period, particularly preterm gestations. Specific advantages and limitations of rabbits in such studies are discussed.
Leukocyte adhesion molecule (LAM) blockade reduces ischemia-reperfusion injury. We tested the hypothesis that a monoclonal antibody (MAb) that recognizes a functional epitope of L-selectin would decrease hemorrhagic shock-induced reperfusion injury. Anesthetized rabbits were subjected to 2 h of hemorrhagic shock (cardiac output reduced to 30% of baseline), then given one of the following treatments: MAbs that recognize functional domains of L-selectin (LAM1-3), CD18 (60.3), MAbs that recognize a nonfunctional domain on L-selectin (LAM1-14), or saline, immediately before resuscitation with shed blood. Additional fluids were administered as needed to maintain cardiac output at baseline levels for 6 h. The cumulative fluid resuscitation after MAb LAM1-3 (58 +/- 34 ml/kg) was not significantly different from after MAb 60.3 (21 +/- 24 ml/kg) or MAb LAM1-14 (66 +/- 51 ml/kg), but it was significantly less than saline-treated controls (142 +/- 142 ml/kg). However, two animals treated with MAb LAM1-14 died before 6 h. If their resuscitation volumes are projected to 6 h by linear regression, then the LAM1-14-treated group required significantly greater volume (101 +/- 99 ml/kg) than the MAb LAM1-3-treated group. We conclude that MAbs to a functional domain on L-selectin are protective against reperfusion-injury following hemorrhagic shock.
After Fontan repair in children, we performed a prospective, open-label study to evaluate the effect of amrinone on pulmonary vascular resistance (PVRI). Eight patients who underwent the Fontan repair had baseline arterial pressure, left atrial pressure, central venous pressure, and cardiac output measured postoperatively. Hemodynamic measurements were repeated after amrinone 4.5 mg/kg. The PVRI tended to decrease, but the change was not statistically significant. Although the systemic vascular resistance decreased to 802 +/- 222 from 941 +/- 191 dynes.s.cm-5.m-2 (P < 0.05), mean arterial blood pressure was unchanged. Cardiac index (3.8 +/- 1.2 to 4.7 +/- 1.6 L.min-1.m-2) and stroke volume index (23.6 +/- 6.7 to 30.5 +/- 8.1 mL.beat-1.m-2) increased, and heart rate decreased (160 +/- 21 to 151 +/- 24 bpm) (P < 0.05). Colloid transfusion during amrinone bolus administration was 13.9 mL/kg. The mean serum amrinone concentration was 4.2 micrograms/mL at the end of bolus and clearance was 2.24 mL.kg-1.min-1. Arrhythmias and thrombocytopenia were not noted. We conclude that amrinone administration is effective in increasing cardiac output in children who have undergone a Fontan repair.
The correlations between continuous positive-pressure ventilation-induced antidiuresis/antinatriuresis, atrial transmural pressure, and atrial natriuretic peptide concentrations have not been clarified. The purpose of the present study was to use aggressive hydration to restore atrial transmural pressure during continuous positive-pressure ventilation and to test for correlations of atrial transmural pressure, atrial natriuretic peptide concentration, diuresis, and natriuresis during this intervention. An intrapleural catheter was used to measure atrial transmural pressure in three ways: a) right atrial pressure minus intrapleural pressure, b) left ventricular end-diastolic pressure minus intrapleural pressure, and c) pulmonary artery occlusion pressure minus intrapleural pressure. Hemodynamic, atrial natriuretic peptide concentrations, and renal measurements were made in 12 anesthetized closed-chest dogs during baseline (intermittent positive-pressure ventilation), during continuous positive-pressure ventilation), during continuous positive-pressure ventilation with 10 cm H2O end-expiratory pressure, and during continuous positive-pressure ventilation plus aggressive hydration (approximately 60 mL/kg lactated Ringer's solution). Pearson's correlation matrix was used to generate all possible correlation coefficients between the three atrial transmural pressures, atrial natriuretic peptide concentrations, urine output, and urine sodium excretion.Application of continuous positive-pressure ventilation resulted in a 60% decrease in right atrial transmural pressure (p less than .05), a 51% decrease in left ventricular end-diastolic transmural pressure (p less than .05), and a 26% decrease in pulmonary artery occlusion transmural pressure (p less than .05) from baseline. Plasma atrial natriuretic peptide concentration decreased from 80 +/- 12 (SEM) pg/mL at baseline to 49 +/- 8 pg/mL during continuous positive-pressure ventilation (p less than .05). Both urine output and sodium excretion decreased by 81% (p less than .05). After aggressive hydration with lactated Ringer's solution during continuous positive-pressure ventilation, to restore atrial transmural pressure to baseline, plasma atrial natriuretic peptide concentration returned to baseline values (81 +/- 12 pg/mL) as did urine output and sodium excretion. Correlation indices (r2 values) between transmural pressure, atrial natriuretic peptide concentration, urine output, and sodium excretion ranged from .835 to .994. Multivariate analysis of covariance demonstrated significant (p less than .05) temporal dependence between the three transmural pressures, atrial natriuretic peptide concentration, urine output, and sodium excretion.The results demonstrate that aggressive hydration during continuous positive-pressure ventilation will restore diuresis and natriuresis and that this response correlates significantly with atrial transmural filling pressure and plasma atrial natriuretic peptide concentration.