Scot T. Bateman

Anemia, Blood Loss, and Blood Transfusions in North American Children in the Intensive Care Unit

RATIONALE Minimizing exposure of children to blood products is desirable. OBJECTIVES We aimed to understand anemia development, blood loss, and red blood cell (RBC) transfusions in the pediatric intensive care unit (PICU). METHODS Prospective, multicenter, 6-month observational study in 30 PICUs. Data were collected on consecutive children (<18 yr old) in the PICU for 48 hours or more. MEASUREMENTS AND MAIN RESULTS Anemia development, blood loss, and RBC transfusions were measured. A total of 977 children were enrolled. Most (74%) children were anemic in the PICU (33% on admission, 41% developed anemia). Blood draws accounted for 73% of daily blood loss; median loss was 5.0 ml/day. Forty-nine percent of children received transfusions; 74% of first transfusions were on Days 1-2. After adjusting for age and illness severity, compared with nontransfused children, children who underwent transfusion had significantly longer days of mechanical ventilation (2.1 d, P < 0.001) and PICU stay (1.8 d, P = 0.03), and had increased mortality (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.43-90.9; P = 0.02), nosocomial infections (OR, 1.9; 95% CI, 1.2-3.0; P = 0.004), and cardiorespiratory dysfunction (OR, 2.1; 95% CI, 1.5-3.0; P < 0.001). High blood loss per kilogram body weight from blood draws (OR, 1.11; 95% CI, 1.03-1.2; P = 0.01) was associated with RBC transfusion more than 48 hours after admission. The most common indication for transfusion was low hemoglobin (42%). Pretransfusion hemoglobin values varied greatly (mean, 9.7 +/- 2.7 g/dl). CONCLUSIONS Critically ill children are at significant risk for developing anemia and receiving blood transfusions. Transfusion in the PICU was associated with worse outcomes. It is imperative to minimize blood loss from blood draws and to set clear transfusion thresholds.

Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study

IntroductionTransfusion is a common treatment in pediatric intensive care units (PICUs). Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome of critically ill children.MethodsProspective, observational study conducted in 30 North American centers, in consecutive patients aged <18 years with a stay ≥ 48 hours in a PICU. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and PICU length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model.ResultsThe median length of storage was 14 days in 296 patients with documented length of storage. For patients receiving blood stored ≥ 14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, P = 0.03). There was also a significant difference in the total PICU length of stay (adjusted median difference +3.7 days, P < 0.001) and no significant change in mortality.ConclusionsIn critically ill children, transfusion of red blood cell units stored for ≥ 14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay.

Early High-Frequency Oscillatory Ventilation in Pediatric Acute Respiratory Failure. A Propensity Score Analysis

RATIONALE The use of high-frequency oscillatory ventilation (HFOV) for acute respiratory failure in children is prevalent despite the lack of efficacy data. OBJECTIVES To compare the outcomes of patients with acute respiratory failure managed with HFOV within 24-48 hours of endotracheal intubation with those receiving conventional mechanical ventilation (CMV) and/or late HFOV. METHODS This is a secondary analysis of data from the RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) study, a prospective cluster randomized clinical trial conducted between 2009 and 2013 in 31 U.S. pediatric intensive care units. Propensity score analysis, including degree of hypoxia in the model, compared the duration of mechanical ventilation and mortality of patients treated with early HFOV matched with those treated with CMV/late HFOV. MEASUREMENTS AND MAIN RESULTS Among 2,449 subjects enrolled in RESTORE, 353 patients (14%) were ever supported on HFOV, of which 210 (59%) had HFOV initiated within 24-48 hours of intubation. The propensity score model predicting the probability of receiving early HFOV included 1,064 patients (181 early HFOV vs. 883 CMV/late HFOV) with significant hypoxia (oxygenation index ≥ 8). The degree of hypoxia was the most significant contributor to the propensity score model. After adjusting for risk category, early HFOV use was associated with a longer duration of mechanical ventilation (hazard ratio, 0.75; 95% confidence interval, 0.64-0.89; P = 0.001) but not with mortality (odds ratio, 1.28; 95% confidence interval, 0.92-1.79; P = 0.15) compared with CMV/late HFOV. CONCLUSIONS In adjusted models including important oxygenation variables, early HFOV was associated with a longer duration of mechanical ventilation. These analyses make supporting the current approach to HFOV less convincing.

Toddlers requiring pediatric intensive care unit admission following at-home exposure to buprenorphine/naloxone

Background: Sublingual buprenorphine is an alternative to methadone for office-based treatment of opioid dependence. Recent reports have examined a growing number of unintentional buprenorphine exposures in children resulting in significant toxicity, even after a single lick or taste of a sublingual tablet. Here, we report a series of unintentional buprenorphine exposures in toddlers over a 2.5-yr period that led to admission to the pediatric intensive care unit. Objectives: The goals of this study were to determine: 1) the prevalence of symptomatic buprenorphine exposure in children <3 yrs of age; 2) the severity of toxicity associated with such exposures; and 3) effective clinical interventions. Methods and Main Results: A retrospective case review was performed on records from the pediatric intensive care unit at an academic medical center located in the northeastern United States. Unintentional buprenorphine/naloxone exposure (n = 9) accounted for the largest single fraction of toxic ingestions among patients younger than 3 yrs within the study period (9/33, 27%). All exposures occurred at the childs place of residence (n = 9, 100%). Clinical signs of opioid toxicity were evident in all nine cases, with the most common symptom being drowsiness or lethargy (n = 9, 100%), followed by miosis (n = 6, 67%) and respiratory depression (n = 5, 56%). Six patients were effectively treated with naloxone (n = 6, 67%). Conclusions: The increased use and similarity to candy of the current formulation of buprenorphine pose a special risk to children, especially toddlers. Buprenorphine exposure in children <3 yrs old can cause significant opioid toxidrome. Naloxone is an effective agent for reversal of symptoms; however, given buprenorphines high affinity and long action, higher doses or continuous infusion may be required. Adults on buprenorphine should be educated on the risks posed to young children in their household and the appropriate storage of medication.

Identifying factors to minimize phlebotomy-induced blood loss in the pediatric intensive care unit.

Objective: Phlebotomy-induced blood loss in critically ill children is common, contributes to anemia, and may be avoidable. We aimed to identify factors associated with phlebotomy-induced blood loss. Design: Prospective observational study, single-center tertiary childrens hospital. Setting: Pediatric intensive care unit. Patients: A total of 63 patients admitted to the pediatric intensive care unit for >48 hrs from 2004 to 2005. Interventions: None. Measurements and Main Results: Phlebotomy resulted in a mean blood volume loss of 2.5 ± 1.4 mL per draw, 7.1 ± 5.3 mL per day, and 34 ± 37 mL per pediatric intensive care unit stay, of which 1.4 ± 1.1 mL per draw, 3.8 ± 3.6 mL per day, and 23 ± 31 mL per pediatric intensive care unit stay were discarded as excess. This excess represents 210% ± 174% of the volume requested by the laboratory and a 110% overdraw. Blood drawn from central venous catheters had significantly greater overdraw volumes, 254% ± 112%, compared to those of arterial, 168% ± 44%, and peripheral intravenous catheters, 143% ± 39%, p < .001. Blood draws sent for one test had an associated overdraw of 278% ± 81%, compared to draws sent for two, 168% ± 48%, three 173% ± 4%, and four or greater tests 55% ± 5%, p < .001. Patients <10 kg had significantly greater mean volumes of blood loss/kg/day compared to patients ≥10 kg, p < .001. Conclusion: Blood drawn in excess of phlebotomy requirements exceeds the blood volume loss drawn for phlebotomy by two fold. Using indwelling catheters for phlebotomy often requires a discard volume to be drawn before obtaining the laboratory sample. Consolidating phlebotomy tests and using a closed system may decrease the amount of blood overdrawn and minimize overall phlebotomy-induced blood loss.

Critically ill children: to transfuse or not to transfuse packed red blood cells, that is the question.

Objectives: This article summarizes the current data on packed red blood cell transfusion in the pediatric intensive care unit setting to help providers make evidence-based decisions regarding packed red blood cell transfusions. Data Sources: Review of the literature, including PubMed, citations from relevant articles, and some articles that have been particularly relevant in adult critical care practice regarding packed red blood cell transfusion. Conclusions: The use of packed red blood cell transfusions is common in the pediatric intensive care unit setting. However, until recently there have been little data to guide providers in this practice. Studies in adult intensive care units have shown less favorable outcomes in patients who received packed red blood cell transfusions. This has led to renewed questioning of the practice of packed red blood cell transfusion in critically ill pediatric patients. New data indicate that using a hemoglobin transfusion threshold of >7 g/dL does not yield improved outcomes. Furthermore, smaller studies have suggested that pediatric intensive care unit patients may be at an increased risk for morbidity and mortality when undergoing transfusion.

Poisonings requiring admission to the pediatric intensive care unit: A 5-year review

Abstract Background. Poisonings represent a significant number of preventable admissions to the pediatric intensive care unit (PICU), but data about poisonings requiring PICU-level care are limited. Objectives. To identify the demographics of patients admitted with poisonings and characterize their clinical courses related to their poisoning. Methods. All poisonings over a 5-year period (2008–2012) at an academic medical center in New England were retrospectively reviewed using electronic medical records in an observational case series. Poisonings were identified using key search terms within an admissions database. Results. There were 273 admissions for poisonings, which represent 8% of total PICU admissions over this time period. The poisonings were unintentional in 148 (54%) cases and intentional in 125 (46%). The vast majority of poisonings occurred in patients either 3 years or below (N = 121, 44%) or 13 years or above (N = 124, 45%). Most (96%) admissions were for less than 48 h and 41% were for less than 24 h. Mean PICU length of stay was 1.2 + 0.7 days. A total of 468 substances were ingested in 54 different drug classes, with analgesics and antidepressants being the most common. Eighty-five (31%) poisonings were polypharmaceutical. The most commonly used therapies were naloxone, activated charcoal, and benzodiazepines. Twenty-seven patients (10%) received mechanical ventilation. There was one fatality, an adolescent with a polypharmacy overdose in a suicide attempt. Conclusion. Pediatric poisonings are a significant percentage of admissions to the PICU. The majority of poisonings are non-fatal, require supportive care, close monitoring, and some specific treatment. Drug classes causing poisonings have changed to a higher percentage of opioids in younger patients and atypical antidepressants in adolescents.

Isoflurane for life-threatening bronchospasm: a 15-year single-center experience.

BACKGROUND: Children with severe bronchospasm requiring mechanical ventilation may become refractory to conventional therapy. In these critically ill patients, isoflurane is an inhaled anesthetic agent available in some centers to treat bronchospasm. We hypothesized that isoflurane is safe and would lead to improved gas exchange in children with life-threatening bronchospasm refractory to conventional therapy. METHODS: A retrospective review was conducted and included mechanically ventilated children treated with isoflurane in a quaternary pediatric ICU for life-threatening bronchospasm, from 1993 to 2007. Demographic, blood gas, ventilator, and outcome data were collected. RESULTS: Thirty-one patients, with a mean age of 9.5 years (range 0.4–23 years) were treated with isoflurane, from 1993 to 2007. Mean time to initiation of isoflurane after intubation was 13 hours (0–120 h), and the mean maximum isoflurane dose was 1.1% (0.3–2.5%). Mean duration of isoflurane administration was 54.5 hours (range 1–181 h), with a total mean duration of mechanical ventilation of 252 hours (range 16–1,444 h). Isoflurane led to significant improvement in pH and PCO2 within 4 hours of initiation (P ≤ .001). Complications during isoflurane administration included hypotension requiring vasoactive infusions in 24 (77%), arrhythmia in 3 (10%), neurologic side effects in 3 (10%), and pneumothorax in 1 (3%) patient. CONCLUSIONS: Isoflurane led to improvement in pH and PCO2 within 4 hours in this series of mechanically ventilated patients with life-threatening bronchospasm. The majority of patients in this series developed hypotension, but there was a low incidence of other side effects related to isoflurane administration. Isoflurane appears to be an effective therapy in patients with life-threatening bronchospasm refractory to conventional therapy. However, further investigation is warranted, given the uncertain overall impact of isoflurane in this context.

Patterns of Sedation Weaning in Critically Ill Children Recovering From Acute Respiratory Failure.

Objective: To characterize sedation weaning patterns in typical practice settings among children recovering from critical illness. Design: A descriptive secondary analysis of data that were prospectively collected during the prerandomization phase (January to July 2009) of a clinical trial of sedation management. Setting: Twenty-two PICUs across the United States. Patients: The sample included 145 patients, aged 2 weeks to 17 years, mechanically ventilated for acute respiratory failure who received at least five consecutive days of opioid exposure. Interventions: None. Measurements and Main Results: Group comparisons were made between patients with an intermittent weaning pattern, defined as a 20% or greater increase in daily opioid dose after the start of weaning, and the remaining patients defined as having a steady weaning pattern. Demographic and clinical characteristics, tolerance to sedatives, and iatrogenic withdrawal symptoms were evaluated. Sixty-six patients (46%) were intermittently weaned; 79 patients were steadily weaned. Prior to weaning, intermittently weaned patients received higher peak and cumulative doses and longer exposures to opioids and benzodiazepines, demonstrated more sedative tolerance (58% vs 41%), and received more chloral hydrate and barbiturates compared with steadily weaned patients. During weaning, intermittently weaned patients assessed for withdrawal had a higher incidence of Withdrawal Assessment Tool-version 1 scores of greater than or equal to 3 (85% vs 46%) and received more sedative classes compared with steadily weaned patients. Conclusions: This study characterizes sedative administration practices for pediatric patients prior to and during weaning from sedation after critical illness. It provides a novel methodology for describing weaning in an at-risk pediatric population that may be helpful in future research on weaning strategies to prevent iatrogenic withdrawal syndrome.

Optimizing intrapulmonary perfluorocarbon distribution: fluoroscopic comparison of mode of ventilation and body position.

ObjectivePartial liquid ventilation with the perfluorochemical, perflubron, has been shown to improve lung mechanics and enhance gas exchange in the treatment of severe acute lung injury. However, the most effective strategy to provide optimal intrapulmonary distribution of perflubron has not been fully accessed. The objective of this study was to examine the effect of body position (supine vs. rotational) and mode of ventilation (conventional mechanical ventilation [CMV] vs. high-frequency oscillatory ventilation [HFOV]) on perflubron distribution and oxygenation improvement. DesignProspective, randomized, animal trial. SettingResearch laboratory at a university medical center. SubjectsTwenty healthy piglets (4.5–6.6 kg). InterventionsSubjects underwent repetitive saline lavage to achieve a uniform degree of lung injury and then were randomized to either CMV or were converted to HFOV. Within each ventilator group, animals were randomized to supine positioning (S) or rotational positioning with alternation between supine and prone position (R) during incremental dosing of three 5-mL/kg doses of perflubron. Measurements and Main Results Arterial blood gas tensions, hemodynamic variables, and the oxygenation index were recorded after each dose of 5 mL/kg. Lateral cinefluoroscopic images after each dose were digitized for computer analysis of density. A density index was calculated for a 2-cm2 window in three dorsal and three ventral lung regions. Uniformity of distribution was calculated by comparing the mean density among the six regions. Oxygenation improvements were compared between groups. There were no significant differences in hemodynamic variables or gas exchange after lung injury in the four groups. Rotational positioning produced significantly more uniform perflubron distribution during both CMV and HFOV. This effect was independent of the mode of ventilation. The mean ventral density index was affected by rotating position and HFOV mode of ventilation after 10 mL/kg of perflubron, and rotating position was affected only after 15 mL/kg of perflubron. There was a significant reduction in the oxygenation index from baseline to end lavage in both CMV groups, as well as all of the animals that were rotated. ConclusionPerflubron is more uniformly dispersed when dosed in a rotational fashion with alternation between supine and prone position during incremental dosing. This effect is independent of mode of ventilation. There was no relationship between oxygenation improvements and nondependent perflubron distribution. CMV and rotating dosing both led to a significant decrease in the oxygenation index after a 15 mL/kg dose of perflubron. This information has important impact on the future development of dosing strategies and clinical trial design.