Susan L. Bratton

Acute Lung Injury in Isolated Traumatic Brain Injury

OBJECTIVE To determine the incidence of acute lung injury (ALI) in comatose patients after isolated traumatic brain injury, to determine whether specific brain lesions diagnosed by cranial computed tomographic scans are associated with ALI, and to determine the outcome of patients with head injuries who developed ALI. METHODS Descriptive epidemiology and a case-control study using the Traumatic Coma Data Bank was performed to evaluate clinical features and brain lesions associated with ALI in patients with isolated head trauma. Patients with ALI were defined as those who demonstrated a ratio of partial pressure of arterial oxygen to fractional expired oxygen of 300 or less. RESULTS Twenty of 100 comatose patients developed ALI. Patients with ALI were almost three times more likely to die or survive in a vegetative state (odds ratio, 2.8; 95% confidence interval, 1.6-4.9). Specific anatomic brain lesions diagnosed by cranial computed tomographic scans were not associated with ALI. However, patients with more severe injuries, i.e., large nonevacuated mass lesions, and those with midline shift demonstrated a 10- and 5-fold increased risk of ALI (odds ratio, 9.9; 95% confidence interval, 1.2-217.1; and odds ratio, 5.5; 95% confidence interval, 1.5-20.0). CONCLUSIONS ALI was common in comatose victims with an isolated traumatic brain injury and was associated with an increased risk of death or a severe neurological morbidity. ALI was associated with the global severity of head injury but not with specific anatomic lesions diagnosed by cranial computed tomographic scans.

Clearance of Morphine in Postoperative Infants During Intravenous Infusion: The Influence of Age and Surgery

We analyzed morphine clearance values in infants receiving the drug by continuous IV infusion for analgesia after surgery, because we found lower steady-state morphine concentrations than we expected from our previous studies. Infants received morphine after a loading dose of 0.05 mg/kg and continuous infusion calculated to reach a steady-state concentration of 20 ng/mL. Blood was sampled twice on Postoperative Day 1 at times separated by at least 2 h, and morphine and morphine-6-glucuronide (M-6-G) concentrations were determined by high-performance liquid chromatography. Clearance of morphine was calculated as infusion rate divided by the steady-state morphine concentration. Morphine given to 26 infants by continuous IV infusion after major noncardiac surgery has rapidly increasing clearance values, from a median value of 9.2 mL [center dot] min-1 [center dot] kg-1 in infants 1-7 days old, 25.3 in infants 31-90 days old, and 31.0 in infants 91-180 days old to 48.9 in infants 180-380 days old. Adult clearance values are reached by 1 mo of age, more quickly than in infants of the same age previously studied who received morphine after cardiac surgeries. M-6-G was measured in all infants. The ratio of M-6-G to morphine concentrations was 1.9-2.1 in these infants, which is lower than ratios reported in older infants or adults by others, but higher than those reported in newborns. Infants with normal cardiovascular systems undergoing surgery clear morphine more efficiently than infants of the same age undergoing cardiac surgery. Implications: Morphine removal from the body is slow in newborns but increases to reach adult values in the first months of life. Calculating the clearance of morphine from blood samples drawn during continuous IV infusions after surgery shows that this maturation occurs more quickly in infants undergoing noncardiac surgery (by 1-3 mo of age) than in those receiving morphine after cardiac surgery (by 6-12 mo of age). (Anesth Analg 1998;86:958-63)

Survival after extracorporeal cardiopulmonary resuscitation in infants and children with heart disease

OBJECTIVE We investigated survival and predictors of mortality for infants and children with heart disease treated with extracorporeal membrane oxygenation as an aid to cardiopulmonary resuscitation. METHODS Children (<18 years) with heart disease who received extracorporeal cardiopulmonary resuscitation and were reported to the Extracorporeal Life Support Organization database were evaluated. Patients were classified into one of 3 groups based on underlying cardiac physiology: single ventricle, 2 ventricles, and cardiac muscle disease. Patients with eligible procedure codes were assigned a Risk Adjustment for Congenital Heart Surgery-1 classification. RESULTS Four hundred ninety-two patients were eligible for analysis, and 279 (57%) were assigned a Risk Adjustment for Congenital Heart Surgery-1 category. Overall survival was 42%. In a multivariable logistic regression analysis, significant pre-extracorporeal predictors for mortality included single-ventricle physiology (odds ratio, 1.6; 95% confidence interval, 1.05-2.4), a history of a stage 1-type procedure (odds ratio, 2.7; 95% confidence interval, 1.2-6.2), and extreme acidosis (arterial blood gas pH < 7.01; odds ratio, 2.2; 95% confidence interval, 1.3-3.7). Right carotid artery cannulation was associated with decreased mortality risk (odds ratio, 0.6; 95% confidence interval, 0.4-0.9). During extracorporeal support, complications, including renal injury, evidence of neurologic injury, and persistent acidosis, were associated with an increased risk of hospital mortality. CONCLUSION Use of extracorporeal membrane oxygenation as an adjunct to cardiopulmonary resuscitation resulted in hospital survival in 42% of infants and children with heart disease. Underlying cardiac physiology and associated cardiac surgical procedures influenced mortality, as did pre-extracorporeal resuscitation status and extracorporeal membrane oxygenation-associated complications.

Colloid volume expanders : Problems, pitfalls and possibilities

SummaryColloid solutions have been developed and used over the past 70 years as expanders of the intravascular space, based on an understanding of Starling’s law. Increasing osmotic pressure with colloidal products has remained an attractive theoretical premise for volume resuscitation. Indeed, colloids have been shown to increase osmotic pressure in clinical practice; however, the effects are shortlived. Lower molecular weight colloids exert a larger initial osmotic effect, but are rapidly cleared from the circulation. Larger molecules exert a smaller osmotic pressure that is sustained longer.The main drawback to colloid therapy lies in pathological states with endothelial injury and capillary leak, precisely the clinical scenario where colloids are commonly given. The colloid solution may leak into the interstitium and remain there exerting an osmotic gradient, pulling additional water into the interstitium.There are 4 general types of colloid products available for clinical use. Albumin is the predominant plasma protein and remains the standard against which other colloids are compared. Albumin, pooled from human donors, is in short supply and remains expensive. Dextrans have been used to prevent deep venous thrombosis and to lower blood viscosity during surgery. Hetastarch has been widely used as a plasma volume expander. It provides equivalent plasma volume expansion to albumin, but has been shown to alter clotting parameters in studies (prolonging the activated partial thromboplastin time and prothrombin time). Although severe coagulopathies have been reported in sporadic cases, hetastarch has not been shown to increase postoperative bleeding compared with albumin therapy, even in large doses (3 L/day).Despite some theoretical advantages compared with crystalloid therapy, colloid administration has not been shown to decrease the risk of acute lung injury or to improve survival. Specific indications for colloid products include hypoproteinaemic or malnourished states, patients who require plasma volume expansion who are unable to tolerate larger amounts of fluid, orthopaedic and reconstructive procedures requiring prevention of thrombus formation and leukapheresis.

Outcome of children who require mechanical ventilatory support after bone marrow transplantation

Objective: To identify clinically measurable factors that could predict outcome for pediatric patients undergoing mechanical ventilatory support after bone marrow transplant. Design: Cohort study. Setting: A referral center for bone marrow transplant patients in Seattle, Washington. Patients: Children <17 yrs old who received a bone marrow transplant and subsequently required mechanical ventilatory support for ≥24 hrs between 1983 and 1996. Interventions: None. Measurements and Main Results: Data were abstracted from the charts of 121 pediatric patients who received a bone marrow transplant and subsequently required mechanical ventilatory support. A total of 19 patients (16%) survived to be extubated and survived for ≥30 days postextubation. Major risk factors for death included respiratory failure as the reason for endotracheal intubation (4% survival), the presence of pulmonary infection (6% survival), and impairment of more than one organ system (2% survival if more than one organ system was dysfunctional on day 7 postintubation). Conclusions: Although the prognosis generally is poor among pediatric bone marrow transplant recipients who subsequently require mechanical ventilatory support, there appear to be some groups within this population in whom the likelihood of survival is close to 0. Because the chance of survival was so small for children with dysfunction of more than one organ system on day 7 after intubation, a recommendation to limit medical support for these children could be considered pending the results of other studies.

Coagulation Tests During Cardiopulmonary Bypass Correlate With Blood Loss in Children Undergoing Cardiac Surgery

OBJECTIVES 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. DESIGN Prospective. SETTING University-affiliated, pediatric medical center. PARTICIPANTS Four hundred ninety-four children. INTERVENTIONS Coagulation tests. MEASUREMENTS AND MAIN RESULTS 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). CONCLUSIONS 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.

Intravenous morphine in postoperative infants: intermittent bolus dosing versus targeted continuous infusions

&NA; Eighty‐three infants received i.v. morphine following surgery as a continuous infusion to a targeted morphine concentration of 20 ng ml−1 (n=56) or as intermittent bolus doses as needed (n=27). Ventilation was compared in the two groups by continuous pulse oximetry, by venous blood gases on postoperative day 1 (POD1) and by CO2 response curves. Infant pain scores were done to assess analgesia every 4 h. Both groups achieved pain scores consistent with analgesia but the bolus group showed a higher percentage of pain scores indicating distress (32 vs. 13%, P<0.001). Room air saturations of <90% were seen for 2.3% of POD1 in infusion‐treated infants and for 2.5% of POD1 in bolus‐treated infants. Mean venous PCO2s were normal in the two groups. Four infants showed ventilatory effects in the infusion group (4/56=7%); venous hypercarbia in two (2 days, 36 days), oximetry desaturation in one (240 days), both effects in one (6 days). Ventilatory effects were not statistically different between the intermittent bolus‐treated and infusion‐treated infants but may be clinically important. Monitoring with continuous oximetry is necessary. Morphine clearance increased with age. Infants with detectable morphine also had measurable morphine‐6‐glucuronide in both groups. Oral intake began at 16 h in both groups and other side effects were infrequent.

Association between age and blood loss in children undergoing open heart operations

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

High-frequency oscillatory ventilation with partial liquid ventilation in a model of acute respiratory failure.

OBJECTIVE To determine whether there is an improvement in oxygenation when partial liquid ventilation and high-frequency oscillatory ventilation are combined in the treatment of acute lung injury, compared with high-frequency oscillatory ventilation alone. DESIGN Controlled animal trial. SETTING Research laboratory in a university setting. SUBJECTS Ten 3-kg piglets. INTERVENTIONS Anesthetized piglets underwent high-frequency oscillatory ventilation, with mean airway pressure of 20 cm H2O, before induction of acute lung injury with repeated saline lavage. When PaO2 values were < 100 torr (< 13.3 kPa), five animals were randomized to receive escalating doses (3, 15, and 30 mL/kg) of perflubron at 60-min intervals. The other five animals remained on high-frequency oscillatory ventilation only. Sham dosing was performed at 60-min intervals in these animals. Arterial blood gases were obtained in both groups at baseline, after injury, and after perflubron and sham doses. MEASUREMENTS AND MAIN RESULTS Statistically significant improvements in oxygenation were demonstrated in animals that received 3 mL/kg of perflubron with high-frequency oscillatory ventilation compared with animals receiving high-frequency oscillatory ventilation alone (253 +/- 161 vs. 90 +/- 30 torr [33.65 +/- 21.46 vs. 12.0 +/- 4.0 kPa], p < .05). Improvements in oxygenation with additional administration of perflubron were not greater than the improvements seen in the high-frequency oscillatory ventilation-only group. PaCO2 and pH were similar in both groups at all times. No hemodynamic compromise occurred in either group of animals. CONCLUSIONS The combination of low-dose perflubron with high-frequency oscillatory ventilation leads to more rapid improvement in arterial oxygenation than high-frequency oscillatory ventilation alone, in a piglet model of acute lung injury. Although the group receiving high-frequency oscillatory ventilation alone eventually achieved PaO2 values that were equivalent to the group receiving high-frequency ventilation and perflubron, the combination of perflubron with high-frequency oscillatory ventilation may permit effective oxygenation and ventilation at lower mean airway pressures by facilitating alveolar expansion and decreasing intrapulmonary shunt.

Efficacy of ϵ-aminocaproic acid in children undergoing cardiac surgery

Abstract Objective: To compare coagulation test results, blood loss, and blood product transfusions between patients receiving prophylactic ϵ-aminocaproic acid (EACA) and a control group matched for age, resternotomy, and surgery in children undergoing cardiac surgery. Design: Nested case-control study. Setting: University-affiliated, pediatric medical center. Participants: Same study period; 70 patients in EACA group and 70 patients in control group. Interventions: 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). Measurements and Main Results: 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 Conclusion: 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.