Peter M. Luckett

High-frequency oscillatory ventilation in pediatric respiratory failure: A multicenter experience

ObjectiveThe use of high-frequency oscillatory ventilation (HFOV) has increased dramatically in the management of respiratory failure in pediatric patients. We surveyed ten pediatric centers that frequently use high-frequency oscillation to describe current clinical practice and to examine factors related to improved outcomes. DesignRetrospective, observational questionnaire study. SettingTen tertiary care pediatric intensive care units. PatientsTwo hundred ninety patients managed with HFOV between January 1997 and June 1998. InterventionsNone. Measurements and Main ResultsPatients were classified according to presence or absence of preexisting lung disease, symptomatic respiratory syncytial virus infection, or presence of cyanotic heart disease or residual right-to-left intracardiac shunt. In addition, patients for whom HFOV acutely failed were analyzed separately. Those patients with preexisting lung disease were significantly smaller, had a significantly higher incidence of pulmonary infection as the triggering etiology, and had a significantly greater duration of conventional ventilation before institution of HFOV compared with patients without preexisting lung disease. Stepwise logistic regression was used to predict mortality and the occurrence of chronic lung disease in survivors. In patients without preexisting lung disease, the model predicted a 70% probability of death when the oxygenation index (OI) after 24 hrs was 28 in the immunocompromised patients and 64 in the patients without immunocompromise. In the immunocompromised patients, the model predicted a 90% probability of death when the OI after 24 hrs was 58. In survivors without preexisting lung disease, the model predicted a 70% probability of developing chronic lung disease when the OI at 24 hrs was 31 in the patients with sepsis syndrome and 50 in the patients without sepsis syndrome. In the patients with sepsis syndrome, the model predicted a 90% probability of developing chronic lung disease when the OI at 24 hrs was 45. ConclusionsGiven the number of centers involved and the size of the database, we feel that our results broadly reflect current practice in the use of HFOV in pediatric patients. These results may help in deciding which patients are most likely to benefit from aggressive intervention by using extracorporeal techniques and may help identify high-risk populations appropriate for prospective study of innovative modes of supporting gas exchange (e.g., partial liquid breathing or intratracheal pulmonary ventilation).

Heart rate variability after acute traumatic brain injury in children.

ObjectiveTo evaluate heart rate variability (HRV) by power spectral analysis of heart rate and its relationship to intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcomes in children with acute traumatic head injury. DesignProspective, case series. SettingPediatric intensive care unit in a level II trauma center/children’s hospital. SubjectsFifteen critically ill children with documented acute traumatic brain injury and four control subjects. InterventionsNone. Measurements and Main ResultsThe normalized total power from 0.04 to 0.15 Hz was used to quantify low-frequency HRV and from 0.15 to 0.40 Hz to quantify high-frequency HRV. The ratio of low- to high-frequency (LF/HF) power was used as a measure of sympathetic modulation of heart rate. The power spectral data from the 5-min samples were averaged over each hour of data collection, and an hourly LF/HF ratio was obtained based on a 60-min electrocardiogram collection (twelve 5-min segments). The daily mean LF/HF ratio was calculated from the hourly LF/HF measurements. We found no linear correlation between the LF/HF ratio and either ICP or CPP (p = NS). There was a significant decrease in the LF/HF ratio when the intracranial pressure was >30 mm Hg (p < .001) or the cerebral perfusion pressure was <40 mm Hg (p < .001). Children with a Glasgow Coma Scale score of 3–4 had a lower LF/HF ratio compared with those who had a Glasgow Coma Scale score of 5–8 (p < .005). Patients who progressed to brain death had a markedly lower LF/HF ratio (p < .001), with a significant decrease after the first 4 hrs of hospitalization. Patients with more favorable outcomes had significantly higher LF/HF ratios. ConclusionsOur findings suggest that an ICP of >30 mm Hg or a CPP of <40 mm Hg may be associated with marked autonomic dysfunction and poor outcome. We speculate that HRV power spectral analysis may be a useful adjunct in determining the severity of neurologic insult and the prognosis for recovery in children. The LF/HF ratio may be helpful not only in identifying those patients who will progress to brain death but also in predicting which patients will have favorable outcomes.

Multicenter Validation of a Computer-Based Clinical Decision Support Tool for Glucose Control in Adult and Pediatric Intensive Care Units

Introduction: Hyperglycemia during critical illness is common, and intravenous insulin therapy (IIT) to normalize blood glucose improves outcomes in selected populations. Methods differ widely in complexity, insulin dosing approaches, efficacy, and rates of hypoglycemia. We developed a simple bedside-computerized decision support protocol (eProtocol-insulin) that yields promising results in the development center. We examined the effectiveness and safety of this tool in six adult and five pediatric intensive care units (ICUs) in other centers. Methods: We required attending physicians of eligible patients to independently intend to use intravenous insulin to normalize blood glucose. We used eProtocol-insulin for glucose control for a duration determined by the clinical caregivers. Adults had an anticipated length of stay of 3 or more days. In pediatric ICUs, we also required support or intended support with mechanical ventilation for greater than 24 hours or with a vasoactive infusion. We recorded all instances in which eProtocol-insulin instructions were not accepted and all blood glucose values. An independent data safety and monitoring board monitored study results and subject safety. Bedside nurses were selected randomly to complete a paper survey describing their perceptions of quality of care and workload related to eProtocol-insulin use. Results: Clinicians accepted 93% of eProtocol-insulin instructions (11,773/12,645) in 100 adult and 48 pediatric subjects. Forty-eight percent of glucose values were in the target range. Both of these results met a priori-defined efficacy thresholds. Only 0.18% of glucose values were ≤40 mg/dl. This is lower than values reported in prior IIT studies. Although nurses reported eProtocol-insulin required as much work as managing a mechanical ventilator, most nurses felt eProtocol-insulin had a low impact on their ability to complete non-IIT nursing activities. Conclusions: A multicenter validation demonstrated that eProtocol-insulin is a valid, exportable tool that can assist clinicians in achieving control of glucose in critically ill adults and children.

Comparison of Intravenous Terbutaline Versus Normal Saline in Pediatric Patients on Continuous High-dose Nebulized Albuterol for Status Asthmaticus

Objective: To determine if the addition of intravenous terbutaline provides any clinical benefit to children with acute severe asthma already on continuous high-dose nebulized albuterol. Methods: We conducted a prospective, randomized, double blind, placebo-controlled trial on pediatric patients with acute severe asthma presenting to a large inner city tertiary childrens emergency department. Consecutive patients between 2 and 17 years of age who failed acute asthma management and needed intensive care unit admission underwent informed consent and were enrolled into the study. Patients not requiring intubation were randomized to receive either intravenous terbutaline or intravenous normal saline while on continuous high-dose nebulized albuterol, ipratropium bromide, and systemic corticosteroids. Outcome measures included a clinical asthma severity score, hours on continuous nebulized albuterol, and duration of stay in the pediatric intensive care unit. In addition, electrocardiograms, electrolytes, lactic acid, and troponin I levels were obtained at routine intervals during the first 24 hours after admission. Patients who significantly worsened while enrolled in the study received intravenous aminophylline according to protocol. Results: Forty-nine patients were enrolled in the study. Patients on terbutaline had a mean improvement in the clinical asthma severity score over the first 24 hours of 6.5 points compared with 4.8 points in the placebo group (P = 0.073). Patients on terbutaline spent 38.19 hours on continuous nebulized albuterol compared with their placebo counterparts who spent 51.93 hours (P = 0.25). The length of stay in the PICU was on average 12.95 hours longer for those patients in the placebo group as compared with the terbutaline group (P = 0.345). One patient was removed from the study for a significant cardiac dysrhythmia. This patient was in the terbutaline group and recovered without complications. Troponin I values at 12 hours and 24 hours were elevated in 3 patients each, all within the terbutaline group. Conclusions: No outcome measures demonstrated statistical significance. Outcome measures revealed a trend toward improvement in the terbutaline group. Before recommending routine use of intravenous terbutaline for acute severe asthma, further study to determine safety and efficacy is necessary.

Cumulative fluid intake minus output is not associated with ventilator weaning duration or extubation outcomes in children

Objective: The effect of fluid balance on respiratory outcomes for critically ill children has not been evaluated. The only indicator of fluid balance routinely recorded across our intensive care units was estimated fluid intake and output. We sought to determine whether cumulative intake minus output (I-O) at the start of weaning predicted weaning duration and whether cumulative I-O at extubation predicted extubation failure. Design: Prospective observational study. Setting: Ten pediatric intensive care units. Patients: Cumulative I-O was recorded daily for 301 mechanically ventilated children (<18 yrs of age) from November 1999 through April 2001. Interventions: Cumulative I-O was recorded during a study of weaning strategies and extubation failure in which mechanical ventilation of the majority of patients during weaning and extubation was managed according to a protocol that did not include fluid balance indicators. Outcomes were the time to successful removal of ventilatory support and the rate of initial extubation failure. Measurements and Main Results: Relationships between cumulative I-O and outcomes were assessed by means of proportional hazards and logistic regression. The mean cumulative I-O per kilogram of ideal body weight at the start of weaning was 101 mL (sd, 180). Cumulative I-O at the time weaning was initiated did not predict duration of mechanical ventilator weaning. The mean cumulative I-O per kilogram of ideal body weight at extubation was 136 mL (sd, 237). Cumulative I-O at extubation did not predict extubation outcome. There was an association between cumulative I-O at extubation and the duration of weaning in cases not managed by a protocol. Conclusion: Although routinely recorded, cumulative fluid I-O does not appear to have clinical utility in cases managed according to a mechanical ventilator protocol in which tidal volume and oxygenation on minimal levels of ventilator support are systematically tested.

Tight glycemic control in critically Ill children

Background In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking. Methods In a 35‐center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower‐target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher‐target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)–free days to day 28. Results The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower‐target group and 353 to the higher‐target group. In the intention‐to‐treat analysis, the median number of ICU‐free days did not differ significantly between the lower‐target group and the higher‐target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per‐protocol analyses, the median time‐weighted average glucose level was significantly lower in the lower‐target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher‐target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower‐target group also had higher rates of health care–associated infections than those in the higher‐target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator‐free days. Conclusions Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF‐PINT ClinicalTrials.gov number, NCT01565941.)

Results of an inner-city school-based asthma and allergy screening pilot study: a combined approach using written questionnaires and step testing

BACKGROUND A questionnaire alone may not be an adequate screening tool for asthma. OBJECTIVE To determine whether an asthma questionnaire used in combination with an exercise step test is better than a questionnaire alone in screening for asthma in children and to evaluate the validity of a rhinitis questionnaire in determining atopy. METHODS The International Study of Asthma and Allergies in Childhood (ISAAC) asthma core questionnaire was used to screen for asthma in 307 inner-city first through third graders. All children who had scores consistent with a diagnosis of asthma underwent step testing, as did a subset of children who had negative overall scores. All children who had inconsistent asthma scores and step test results underwent methacholine challenge testing. The same 307 children underwent rhinitis screening and children who had one or more positive responses on the ISAAC rhinitis questionnaire underwent skin testing as did a subset of children who had all negative responses. RESULTS Three hundred of 307 asthma and rhinitis questionnaires were returned. Twenty-eight children (9%) had global asthma scores that were considered to be positive (5 or above). Twenty-four of these children underwent step testing as did 34 randomly selected children who had negative global asthma scores. Thirty-one (91%) of the 34 children who had negative global asthma scores had negative step tests. Similarly, 20 of 24 children (83%) of the children who had positive global asthma scores had negative step tests. Only 4 children who had positive global asthma scores were step test-positive or had reversible airway obstruction at baseline. Using a positive methacholine challenge as the gold standard for establishing bronchial hyperresponsiveness, the global asthma score derived from the eight-item ISAAC asthma questionnaire yielded a sensitivity of 64%, a specificity of 11%, a positive predictive value of 47%, and a negative predictive value of 20%. Comparing the six-item ISAAC rhinitis questionnaire results to the gold standard, skin test reactivity, the questionnaire yielded a sensitivity of 76%, a specificity of 21%, a positive predictive value of 56%, and a negative predictive value of 40%. CONCLUSIONS Step testing was not useful as a screening tool for asthma. In addition, the ISAAC asthma questionnaire may not be a good asthma screening tool for inner-city pediatric populations, especially if the form is self-administered. Investigators should first validate both the ISAAC asthma and rhinitis screening questionnaires in the particular population to be studied before widespread asthma and allergy screening efforts are initiated using these tools.

Feasibility of asynchronous independent lung high-frequency oscillatory ventilation in the management of acute hypoxemic respiratory failure: A case report

ObjectiveTo report the first case of the use of asynchronous independent lung high-frequency oscillatory ventilation (AIL-HFOV) in the management of acute hypoxemic respiratory failure in a large pediatric patient with markedly asymmetric lung disease. DesignCase study. SettingTertiary pediatric intensive care unit in a pediatric teaching hospital. PatientA 17-yr-old, 87-kg male patient with trisomy 21 and with respiratory failure and progressive hypoxemia because of pneumonia. InterventionsIntubation with a 37-Fr double-lumen endobronchial tube and ventilation with two oscillatory ventilators for a total of 16 days. Measurements and Main ResultsHemodynamic data were obtained using a pulmonary artery catheter. Adequate oxygenation and ventilation were readily achieved after institution of AIL-HFOV. The Fio2/Pao2 ratio increased from 52 to 224, and the shunt fraction decreased from 40 to 9 after 30 mins of AIL-HFOV. Fio2 was rapidly reduced from 1.0 to 0.4 on the right lung and to 0.6 on the left lung. Mean arterial pressure was maintained, the cardiac index increased from 3.5 to 5.4 L/min/m2, the systemic vascular resistance index decreased from 1513 to 1225 dyne·sec/cm5·m2, and the pulmonary vascular resistance index decreased from 723 to 428 dyne·sec/cm5·m2 without the need for additional fluid boluses or increases in inotropic support. No airleaks developed during the entire hospital stay. ConclusionsAIL-HFOV improved oxygenation and hemodynamic performance in this large patient. This case demonstrates that it is feasible to use two high-frequency oscillatory ventilators to independently ventilate the lungs of a large patient with markedly asymmetric lung disease. We believe that AIL-HFOV deserves future study and development for the treatment of large patients with acute hypoxemic respiratory failure and asymmetric lung disease when other choices are limited.

A perspective on early mobilization for adult patients with respiratory failure: Lessons for the pediatric population

OBJECTIVE To summarize the evidence for early mobilization programs in critically ill pediatric and adult patients with respiratory failure. This paper describes our review of the literature and outlines the morbidities associated with immobility, mechanical ventilation and sedation.The clinical management of acutely ill pediatric patients with respiratory failure traditionally consists of mechanical ventilation, sedation and prolonged immobilization. Although the most severely ill patients require these therapies for survival, each therapy comes with adverse consequences. Early mobilization may reduce complications and confer benefit for children with respiratory failure or those who require prolonged mechanical ventilator support. DESIGN Systematic review of the literature pertaining to early mobilization in pediatric and adult patients with respiratory failure. We searched Medline, PubMed, CINAHL and Cochrane database of controlled trials. Randomized controlled trials (RCTs), observational cohort studies, case control studies and population-based analysis were considered for inclusion. Two reviewers (MM and EH) independently selected pertinent studies. RESULTS No studies of early mobilization in pediatric populations were found. Five adult studies were identified for review; two randomized controlled trials and three observational studies. All studies suggested an improvement in morbidity and economic benefit with implementation of early mobilization. CONCLUSIONS Early mobilization in critically ill adult patients with respiratory failure is associated with a decrease in duration of sedatives, ventilator dependant days, ICU and hospital length of stay. The paucity of studies of early mobilization suggest that implementation of early mobilization is not widely practiced. Studies of early mobilization therapy in the adult patient requiring prolonged mechanical ventilator support are reviewed, and the physiologic rational and observed obstacles to integration of an early mobilization program are discussed. The adult data and scientific evidence are combined to support an opinion about the possible benefits of early mobilization programs. The generalizability of the findings and the feasibility of implementing early mobilization in critically ill children who require prolonged mechanical ventilator support are also considered.

The use of pulmonary clearance medications in the acutely ill patient

ABSTRACT Introduction: Retention of airway secretions occurs in disease, leading to airway plugging, atelectasis, and worsened respiratory mechanics, making airway clearance an important therapeutic target. Areas covered: Many medications designed to enhance clearance of airway secretions are available. We will review the medications available to enhance airway clearance, their mechanisms of action, and the evidence available for their use in acutely ill patients. Expert commentary: In the cystic fibrosis (CF) population, beneficial effects have been shown in pulmonary function with the use of some of these agents. In the non-CF population, there is limited evidence regarding these medications. While some studies have found benefit, the quality of evidence is low, making it difficult to draw conclusions. While certain patients may derive benefit, the general use of these medications in acutely ill patients without CF cannot be recommended at this time.