Jeffrey S. Rubenstein

Bispectral index as a guide for titration of propofol during procedural sedation among children.

Objective. To determine whether the bispectral index (BIS) monitor could be used to guide physicians in titrating propofol to an effective safe level of deep sedation for children undergoing painful medical procedures. Design. Multiphase clinical trial. Setting. Outpatient treatment center of a university childrens hospital. Patients. Pediatric outpatients undergoing painful medical procedures. Interventions. Patients were sedated with propofol for the procedures. Patients were monitored with a BIS monitor, and the BIS score was correlated with the patients clinical level of sedation. The BIS score was then used as a guide to titrate propofol in the last phase of the study. Measurements and Main Results. The study consisted of 3 phases. In a chart review of data for 154 children who underwent 212 procedures, propofol was found to be safe and effective, with consistent dosing among the intensivists administering the medication. The children received a mean bolus dose of propofol of 1.56 mg/kg, with a mean total dose of propofol of 0.33 mg/kg per minute for the duration of the procedure. In the second phase, 21 patients ranging in age from 27 weeks to 18 years, with normal neurologic function, were sedated with propofol. An observer who was blinded to the BIS scores recorded clinical levels of sedation and reactivity (with a modified Ramsay scale and reactivity score) every 1 to 3 minutes. Another observer recorded the BIS scores at the same times. A total of 275 data points were collected and evaluated. All data points from the times at which patients were considered to be sedated adequately were used to construct a normal distribution of BIS scores. The mean BIS score was 62. This distribution was used to predict that a maximal BIS score of 47 was needed to ensure adequate sedation for 90% of the population. In the third phase of the study, an algorithm was devised to determine the target BIS score necessary for adequate sedation of 95% of the patients. We chose an initial BIS score of 50 (at which 85% of the patients in phase 2 were sedated) because of the possibility of data from phase 2 being skewed toward oversedation. Propofol was administered by an intensivist in an attempt to maintain the target BIS score. A blinded observer noted the patients clinical level of sedation. In this group, there were 2 failures, ie, patients were clinically uncomfortable despite a BIS score of ≤50, representing only 90% success. Therefore, with the algorithm, propofol was titrated to sedate the next patients to a BIS score of 45. These patients required a mean bolus dose of 1.47 mg/kg and a mean total dose of 0.51 mg/kg per minute to maintain a BIS score of 45. They awakened in 12.75 minutes. All patients were sedated adequately, all procedures were successful, and no patients experienced complications from the sedation. To eliminate variability in the way propofol was dosed, the next 10 patients were given propofol according to a standardized protocol. These 10 children received an initial bolus of 1 mg/kg, with incremental bolus doses of 0.5 mg/kg per dose (maximum: 20 mg) to achieve and to maintain a BIS score of 45. With this protocol, all patients were sedated adequately and none experienced complications from the sedation. The patients required a mean bolus dose of 2.23 mg/kg and a mean dose of 0.52 mg/kg per minute to maintain a BIS score of 45. The mean time until awakening was 14.9 minutes. Regarding the total dose over time and the time until awakening, there was no statistical significance between this group and the group sedated to a BIS score of 45 without the dosing protocol. Conclusion. The BIS monitor can be a useful monitoring guide for the titration of propofol by physicians who are competent in airway and hemodynamic management, to achieve deep sedation for children undergoing painful procedures.

Helping mothers cope with a critically ill child: A pilot test of the COPE intervention

The purpose of this study was to pilot test the effects of a theoretically driven intervention program (COPE = Creating Opportunities for Parent Empowerment) on the coping outcomes of critically ill children and their mothers. Thirty mothers of 1- to 6-year-old children in a pediatric intensive care unit (PICU) were randomly assigned to receive COPE or a comparison program. Mothers who received the COPE program: (a) provided more support to their children during intrusive procedures; (b) provided more emotional support to their children; (c) reported less negative mood state and less parental stress related to their childrens emotions and behaviors; and (d) reported fewer post-traumatic stress symptoms and less parental role change four weeks following hospitalization. Results indicate the need to educate parents regarding their childrens responses as they recover from critical illness and how they can assist their children in coping with the stressful experience.

Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial.

Objectives: Children undergoing cardiac surgery with cardiopulmonary bypass are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells and platelets transfused to these patients will reduce postoperative transfusion-related immune modulation and inflammation. Design: Prospective, randomized, controlled clinical trial. Setting: University hospital pediatric cardiac intensive care unit. Patients: Children from birth to 17 yrs undergoing cardiac surgery with cardiopulmonary bypass. Interventions: Children were randomized to an unwashed or washed red blood cells and platelet transfusion protocol for their surgery and postoperative care. All blood was leuko-reduced, irradiated, and ABO identical. Plasma was obtained for laboratory analysis preoperatively, immediately, and 6 and 12 hrs after cardiopulmonary bypass. Primary outcome was the 12-hr postcardiopulmonary bypass interleukin-6-to-interleukin-10 ratio. Secondary measures were interleukin levels, C-reactive protein, and clinical outcomes. Measurements and Main Results: One hundred sixty-two subjects were studied, 81 per group. Thirty-four subjects (17 per group) did not receive any blood transfusions. Storage duration of blood products was similar between groups. Among transfused subjects, the 12-hr interleukin ratio was significantly lower in the washed group (3.8 vs. 4.8; p = .04) secondary to lower interleukin-6 levels (after cardiopulmonary bypass: 65 vs.100 pg/mL, p = .06; 6 hrs: 89 vs.152 pg/mL, p = .02; 12 hrs: 84 vs.122 pg/mL, p = .09). Postoperative C-reactive protein was lower in subjects receiving washed blood (38 vs. 43 mg/L; p = .03). There was a numerical, but not statistically significant, decrease in total blood product transfusions (203 vs. 260) and mortality (2 vs. 6 deaths) in the washed group compared to the unwashed group. Conclusions: Washed blood transfusions in cardiac surgery reduced inflammatory biomarkers, number of transfusions, donor exposures, and were associated with a nonsignificant trend toward reduced mortality. A larger study powered to test for clinical outcomes is needed to determine whether these laboratory findings are clinically significant.

Children with single-ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: results of a prospective, randomized, controlled trial of a restrictive versus liberal red-cell transfusion strategy.

Objective: To examine the impact of a restrictive vs. liberal transfusion strategy on arterial lactate and oxygen content differences in children with single-ventricle physiology post cavopulmonary connection. Children with single-ventricle physiology are routinely transfused postoperatively to increase systemic oxygen delivery, and transfusion thresholds in this population have not been studied. Design: Prospective, randomized, controlled, clinical trial. Setting: Pediatric cardiac intensive care unit in a teaching hospital. Patients: Infants and children (n = 60) with variations of single-ventricle physiology presenting for cavopulmonary connection. Interventions: Subjects were randomized to a restrictive (hemoglobin of <9.0 g/dL), or liberal (hemoglobin of ≥13.0 g/dL) transfusion strategy for 48 hrs post operation. Primary outcome measures were mean and peak arterial lactate. Secondary end points were arteriovenous (C(a-v)o2) and arteriocerebral oxygen content (C(a-c)o2) differences and clinical outcomes. Measurements and Main Results: A total of 30 children were in each group. There were no significant preoperative differences. Mean hemoglobin in the restrictive and liberal groups were 11 ± 1.3 g/dL and 13.9 ± 0.5 g/dL, respectively (p < .01). No differences in mean (1.4 ± 0.5 mmol/L [Restrictive] vs. 1.4 ± 0.4 mmol/L [Liberal]) or peak (3.1 ± 1.5 mmol/L [Restrictive] vs. 3.2 ± 1.3 mmol/L [Liberal]) lactate between groups were found. Mean number of red blood cell transfusions were 0.43 ± 0.6 and 2.1 ± 1.2 (p < .01), and donor exposure was 1.2 ± 0.7 and 2.4 ± 1.1 to (p < .01), for each group, respectively. No differences were found in C(a-v)o2, C(a-c)o2, or clinical outcome measures. Conclusion: Children with single-ventricle physiology do not benefit from a liberal transfusion strategy after cavopulmonary connection. A restrictive red blood cell transfusion strategy decreases the number of transfusions, donor exposures, and potential risks in these children. Larger studies with clinical outcome measures are needed to determine the transfusion threshold for children post cardiac repair or palliation for congenital heart disease.

Association of pre mortem diagnosis and autopsy findings in pediatric intensive care unit versus emergency department versus ward patients

OBJECTIVE As part of the overall quality assurance program for the Department of Pediatrics, we determined whether there were differences in the rates of unexpected autopsy findings between pediatric intensive care unit (ICU), emergency department, and ward patients. DESIGN Prospective, descriptive study. SETTING Tertiary care childrens hospital. PATIENTS Pediatric deaths (n = 212). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Autopsies were obtained more frequently in emergency department patients (27/29 [93%]) compared with pediatric ICU (88/121 [73%] and ward (42/62 [68%]) patients (p = .03). The medical examiners cases were more frequently from emergency department patients (22/27 [81%]) compared with pediatric ICU (39/88 [44%]) or ward (11/42 [26%]) patients (p < .001). We found unexpected autopsy findings in 19 (12%) of 157 patients. There were no unexpected findings from the medical examiners cases. The most common unexpected findings were unidentified infections (n = 7 [three fungal, three viral, and one nonspecific]) and unrecognized cardiac malformations (n = 4). Unexpected findings occurred more frequently in pediatric ICU patients (16/88 [18%]) vs. emergency department (2/27 [7%]) or ward (1/42 [2%]) patients (p = .03). The occurrence rates of major unexpected findings (Class I and II) in pediatric ICU (7/79 [9%]), emergency department (2/27 [7%]), and ward (1/42 [2%]) patients were similar (p = .4). There were two Goldmans Class I unexpected findings in the pediatric ICU and emergency department patients, and one Goldmans Class I unexpected finding in the ward patients. CONCLUSIONS Autopsies were performed more frequently in emergency department patients. Class I through IV unexpected findings occurred more frequently in pediatric ICU patients compared with emergency department or ward patients. Autopsy examinations are an especially valuable diagnostic tool for pediatric ICU patients and physicians.

Duration of mechanical ventilation in life-threatening pediatric asthma: description of an acute asphyxial subgroup.

Objective. Acute asphyxial asthma (AAA) is well described in adult patients and is characterized by a sudden onset that may rapidly progress to a near-arrest state. Despite the initial severity of AAA, mechanical ventilation often restores gas exchange promptly, resulting in shorter durations of ventilation. We believe that AAA can occur in children and can lead to respiratory failure that requires mechanical ventilation. Furthermore, children with rapid-onset respiratory failure that requires intubation in the emergency department (ED) are more likely to have AAA and a shorter duration of mechanical ventilation than those intubated in the pediatric intensive care unit (PICU). Methods. An 11-year retrospective chart review (1991-2002) was conducted of all children who were aged 2 through 18 years and had the primary diagnosis of status asthmaticus and required mechanical ventilation. Results. During the study period, 33 (11.4%) of 290 PICU admissions for status asthmaticus required mechanical ventilation. Thirteen children presented with rapid respiratory failure en route, on arrival, or within 30 minutes of arrival to the ED versus 20 children who progressed to respiratory failure later in their ED course or in the PICU. Mean duration of mechanical ventilation was significantly shorter in the children who presented with rapid respiratory failure versus those with progressive respiratory failure (29 ± 43 hours vs 88 ± 72 hours). Children with rapid respiratory failure had greater improvements in ventilation and oxygenation than those with progressive respiratory failure as measured by pre- and postintubation changes in arterial carbon dioxide pressure, arterial oxygen pressure/fraction of inspired oxygen ratio, and alveolar-arterial gradient. According to site of intubation, 23 children required intubation in the ED, whereas 10 were intubated later in the PICU. Mean duration of mechanical ventilation was significantly shorter in the ED group versus the PICU group (42 ± 63 hours vs 118 ± 46 hours). There were significantly greater improvements in ventilation and oxygenation in the ED group versus the PICU group as measured by pre- and postintubation changes in arterial carbon dioxide pressure and arterial oxygen pressure/fraction of inspired oxygen ratio. Conclusions. AAA occurs in children and shares characteristics seen in adult counterparts. Need for early intubation is a marker for AAA and may not represent a failure to maximize preintubation therapies. AAA represents a distinct form of life-threatening asthma and requires additional study in children.

Bacterial and fungal colonization of endotracheal tubes in children : a prospective study

ObjectivesTo evaluate both the frequency and route of endotracheal colonization of intubated children by pathogens and to assess the usefulness of Pediatric Risk of Mortality scoring and measurement of gastric pH in predicting this colonization. DesignProspective data collection. SettingA multidisciplinary pediatric ICU. PatientsNineteen children with medical/surgical problems who were intubated for at least 4 days. InterventionsBuccal mucosa, and endotracheal and gastric aspirates were cultured for pathogens immediately after endotracheal intubation and daily for 4 to 5 days. Pediatric Risk of Mortality scores were calculated at the time of endotracheal intubation; gastric pH was measured each time that the cultures were obtained. Measurements and Main ResultsThe buccal mucosae of ten (53%) of 19 children were colonized with Candida species at the time of endotracheal intubation. This colonization correlated with the degree of physiologic instability as measured by Pediatric Risk of Mortality scores (12.9 ± 2.8 SEM for those patients colonized vs. 4.9 ± 1.0 for those patients not colonized; p = .01), but not with preintubation antibiotic therapy. Eleven (58%) children acquired 27 endotracheal pathogens after the day of intubation. The buccal mucosa was the initial site of colonization of 19 (70%) of 27 of the acquired pathogens. A gastric pH of >3.0 at the time of intubation correctly predicted colonization in nine of 11 children (p < .025, Fishers exact test); a Pediatrick Risk of Mortality score of >8 at the time of endotracheal intubation correctly predicted colonization in eight of 11 patients (p < .05, Fishers exact test). ConclusionsColonization of the buccal mucosa appears to be the crucial antecedent to endotracheal colonization in children. In children, gastric pH and Pediatric Risk of Mortality scores at the time of endotracheal intubation can predict pathogenic endotracheal colonization within 4 days of intubation. Selective decontamination regimes may be appropriate for these patients, especially those regimes that are directed to the buccal mucosa.

Chronic treatment with diisopropylfluorophosphate increases dopamine turnover in the striatum of the rat

Following the administration of a single dose of diisopropylfluorophosphate (DFP) there is a rise of acetylcholine (ACh) in the rat striatum and frontal cortex. With chronic treatment, striatal ACh content returns to normal, but frontal cortex ACh remains elevated. In striatum but not frontal cortex, there is a rise of dopamine (DA) content and turnover after chronic DFP treatment. We speculate that DA content and turnover are increased after chronic DFP because the nigrostriatal neuronal feedback loop and local feedback loops are activated to compensate for increased cholinergic tone.

Longer RBC storage duration is associated with increased postoperative infections in pediatric cardiac surgery.

Objectives: Infants and children undergoing open heart surgery routinely require multiple RBC transfusions. Children receiving greater numbers of RBC transfusions have increased postoperative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children. Whether the association of increased transfusions and worse outcomes can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for congenital heart disease is unknown. Interventions: One hundred and twenty-eight consecutively transfused children undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass who were participating in a randomized trial of washed versus standard RBC transfusions were evaluated for an association of RBC storage age and clinical outcomes. To avoid confounding with dose of transfusions and timing of infection versus timing of transfusion, a subgroup analysis of patients only transfused 1–2 units on the day of surgery was performed. Measurements and Main Results: Mortality was low (4.9%) with no association between RBC storage duration and survival. The postoperative infection rate was significantly higher in children receiving the oldest blood (25–38 d) compared with those receiving the freshest RBCs (7–15 d) (34% vs 7%; p = 0.004). Subgroup analysis of subjects receiving only 1–2 RBC transfusions on the day of surgery (n = 74) also demonstrates a greater prevalence of infections in subjects receiving the oldest RBC units (0/33 [0%] with 7- to 15-day storage; 1/21 [5%] with 16- to 24-day storage; and 4/20 [20%] with 25- to 38-day storage; p = 0.01). In multivariate analysis, RBC storage age and corticosteroid administration were the only predictors of postoperative infection. Washing the oldest RBCs (> 27 d) was associated with a higher infection rate and increased morbidity compared with unwashed RBCs. Discussion: Longer RBC storage duration was associated with increased postoperative nosocomial infections. This association may be secondary in part, to the large doses of stored RBCs transfused, from single-donor units. Washing the oldest RBCs was associated with increased morbidity, possibly from increased destruction of older, more fragile erythrocytes incurred by washing procedures. Additional studies examining the effect of RBC storage age on postoperative infection rate in pediatric cardiac surgery are warranted.

Interhospital transport. A pediatric perspective

Interhospital transport of children must not be undertaken in a vacuum. Basic medical ethics and federal laws demand that there be some responsibility in providing adequate care during the transport process, and that this care meets or exceeds the level provided by the referring hospital. The care provided must also be appropriate to the severity of illness of the transported children. National guidelines and standards are needed to establish and coordinate a uniform interhospital transport process for critically ill children.