Ira M. Cheifetz

Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature

BackgroundHigh flow nasal cannula (HFNC) systems utilize higher gas flow rates than standard nasal cannulae. The use of HFNC as a respiratory support modality is increasing in the infant, pediatric, and adult populations as an alternative to non-invasive positive pressure ventilation.ObjectivesThis critical review aims to: (1) appraise available evidence with regard to the utility of HFNC in neonatal, pediatric, and adult patients; (2) review the physiology of HFNC; (3) describe available HFNC systems (online supplement); and (4) review ongoing and planned trials studying the utility of HFNC in various clinical settings.ResultsClinical neonatal studies are limited to premature infants. Only a few pediatric studies have examined the use of HFNC, with most focusing on this modality for viral bronchiolitis. In critically ill adults, most studies have focused on acute respiratory parameters and short-term physiologic outcomes with limited investigations focusing on clinical outcomes such as duration of therapy and need for escalation of ventilatory support. Current evidence demonstrates that HFNC generates positive airway pressure in most circumstances; however, the predominant mechanism of action in relieving respiratory distress is not well established.ConclusionCurrent evidence suggests that HFNC is well tolerated and may be feasible in a subset of patients who require ventilatory support with non-invasive ventilation. However, HFNC has not been demonstrated to be equivalent or superior to non-invasive positive pressure ventilation, and further studies are needed to identify clinical indications for HFNC in patients with moderate to severe respiratory distress.

Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

OBJECTIVE To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. DESIGN Consensus conference of experts in pediatric acute lung injury. SETTING Not applicable. SUBJECTS PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS None. METHODS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. MEASUREMENTS AND MAIN RESULTS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. CONCLUSIONS The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

Active rehabilitation and physical therapy during extracorporeal membrane oxygenation while awaiting lung transplantation: a practical approach.

Objective:Extracorporeal membrane oxygenation as a bridge to lung transplantation has traditionally been associated with substantial morbidity and mortality. A major contributor to these complications may be weakness and overall deconditioning secondary to pretransplant critical illness and immobility. In an attempt to address this issue, we developed a collaborative program to allow for active rehabilitation and physical therapy for patients requiring life support with extracorporeal membrane oxygenation before lung transplantation. Design:An interdisciplinary team responded to an acute need to develop a mechanism for active rehabilitation and physical therapy for patients awaiting lung transplantation while being managed with extracorporeal membrane oxygenation. We describe a series of three patients who benefited from this new approach. Setting:A quaternary care pediatric intensive care unit in a childrens hospital set within an 800-bed university academic hospital with an active lung transplantation program for adolescent and adult patients. Patients, Interventions, and Main Results:Three patients (ages 16, 20, and 24 yrs) with end-stage respiratory failure were rehabilitated while on extracorporeal membrane oxygenation awaiting lung transplantation. These patients were involved in active rehabilitation and physical therapy and, ultimately, were ambulatory on extracorporeal membrane oxygenation before successful transplantation. Following lung transplantation, the patients were liberated from mechanical ventilation, weaned to room air, transitioned out of the intensive care unit, and ambulatory less than 1 wk posttransplant. Conclusions:A comprehensive, multidisciplinary system can be developed to safely allow for active rehabilitation, physical therapy, and ambulation of patients being managed with extracorporeal membrane oxygenation. Such programs may lead to a decreased threshold for the utilization of extracorporeal membrane oxygenation before transplant and have the potential to improve conditioning, decrease resource utilization, and lead to better outcomes in patients who require extracorporeal membrane oxygenation before lung transplantation.

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).

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass

BACKGROUND Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.

Protocolized Sedation vs Usual Care in Pediatric Patients Mechanically Ventilated for Acute Respiratory Failure: A Randomized Clinical Trial

IMPORTANCE Protocolized sedation improves clinical outcomes in critically ill adults, but its effect in children is unknown. OBJECTIVE To determine whether critically ill children managed with a nurse-implemented, goal-directed sedation protocol experience fewer days of mechanical ventilation than patients receiving usual care. DESIGN, SETTING, AND PARTICIPANTS Cluster randomized trial conducted in 31 US pediatric intensive care units (PICUs). A total of 2449 children (mean age, 4.7 years; range, 2 weeks to 17 years) mechanically ventilated for acute respiratory failure were enrolled in 2009-2013 and followed up until 72 hours after opioids were discontinued, 28 days, or hospital discharge. INTERVENTION Intervention PICUs (17 sites; n = 1225 patients) used a protocol that included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; n = 1224 patients) managed sedation per usual care. MAIN OUTCOMES AND MEASURES The primary outcome was duration of mechanical ventilation. Secondary outcomes included time to recovery from acute respiratory failure, duration of weaning from mechanical ventilation, neurological testing, PICU and hospital lengths of stay, in-hospital mortality, sedation-related adverse events, measures of sedative exposure (wakefulness, pain, and agitation), and occurrence of iatrogenic withdrawal. RESULTS Duration of mechanical ventilation was not different between the 2 groups (intervention: median, 6.5 [IQR, 4.1-11.2] days; control: median, 6.5 [IQR, 3.7-12.1] days). Sedation-related adverse events including inadequate pain and sedation management, clinically significant iatrogenic withdrawal, and unplanned endotracheal tube/invasive line removal were not significantly different between the 2 groups. Intervention patients experienced more postextubation stridor (7% vs 4%; P = .03) and fewer stage 2 or worse immobility-related pressure ulcers (<1% vs 2%; P = .001). In exploratory analyses, intervention patients had fewer days of opioid administration (median, 9 [IQR, 5-15] days vs 10 [IQR, 4-21] days; P = .01), were exposed to fewer sedative classes (median, 2 [IQR, 2-3] classes vs 3 [IQR, 2-4] classes; P < .001), and were more often awake and calm while intubated (median, 86% [IQR, 67%-100%] of days vs 75% [IQR, 50%-100%] of days; P = .004) than control patients, respectively; however, intervention patients had more days with any report of a pain score ≥ 4 (median, 50% [IQR, 27%-67%] of days vs 23% [IQR, 0%-46%] of days; P < .001) and any report of agitation (median, 60% [IQR, 33%-80%] vs 40% [IQR, 13%-67%]; P = .003), respectively. CONCLUSIONS AND RELEVANCE Among children undergoing mechanical ventilation for acute respiratory failure, the use of a sedation protocol compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary outcomes suggest a complex relationship among wakefulness, pain, and agitation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00814099.

Deadspace to tidal volume ratio predicts successful extubation in infants and children

Objective Using a modification of the Bohr equation, single-breath carbon dioxide capnography is a noninvasive technology for calculating physiologic dead space (Vd/Vt). The objective of this study was to identify a minimal Vd/Vt value for predicting successful extubation from mechanical ventilation in pediatric patients. Design Prospective, blinded, clinical study. Setting Medical and surgical pediatric intensive care unit of a university hospital. Patients Intubated children ranging in age from 1 wk to 18 yrs. Interventions None. Measurements and Main Results Forty-five patients were identified by the pediatric intensive care unit clinical team as meeting criteria for extubation. Thirty minutes before the planned extubation, each patient was begun on pressure support ventilation set to deliver an exhaled tidal volume of 6 mL/kg. After 20 mins on pressure support ventilation, an arterial blood gas was obtained, Vd/Vt was calculated, and the patient was extubated. Over the next 48 hrs, the clinical team managed the patient without knowledge of the preextubation Vd/Vt value. Of the 45 patients studied, 25 had Vd/Vt ≤0.50. Of these patients, 24 of 25 (96%) were successfully extubated without needing additional ventilatory support. In an intermediate group of patients with Vd/Vt between 0.50 and 0.65, six of ten patients (60%) successfully extubated from mechanical ventilation. However, only two of ten patients (20%) with a Vd/Vt ≥0.65 were successfully extubated. Logistic regression analysis revealed a significant association between lower Vd/Vt and successful extubation. Conclusions A Vd/Vt ≤0.50 reliably predicts successful extubation, whereas a Vd/Vt >0.65 identifies patients at risk for respiratory failure following extubation. There appears to be an intermediate Vd/Vt range (0.51–0.65) that is less predictive of successful extubation. Routine Vd/Vt monitoring of pediatric patients may permit earlier extubation and reduce unexpected extubation failures.

Active Rehabilitation During Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation

BACKGROUND: Patients with end-stage lung disease often progress to critical illness, which dramatically reduces their chance of survival following lung transplantation. Pre-transplant deconditioning has a significant impact on outcomes for all lung transplant patients, and is likely a major contributor to increased mortality in critically ill lung transplant recipients. The aim of this report is to describe a series of patients bridged to lung transplant with extracorporeal membrane oxygenation (ECMO) and to examine the potential impact of active rehabilitation and ambulation during pre-transplant ECMO. METHODS: This retrospective case series reviews all patients bridged to lung transplantation with ECMO at a single tertiary care lung transplant center. Pre-transplant ECMO patients receiving active rehabilitation and ambulation were compared to those patients who were bridged with ECMO but did not receive pre-transplant rehabilitation. RESULTS: Nine consecutive subjects between April 2007 and May 2012 were identified for inclusion. One-year survival for all subjects was 100%, with one subject alive at 4 months post-transplant. The 5 subjects participating in pre-transplant rehabilitation had shorter mean post-transplant mechanical ventilation (4 d vs 34 d, P = .01), ICU stay (11 d vs 45 d, P = .01), and hospital stay (26 d vs 80 d, P = .01). No subject who participated in active rehabilitation had post-transplant myopathy, compared to 3 of 4 subjects who did not participate in pre-transplant rehabilitation on ECMO. CONCLUSIONS: Bridging selected critically ill patients to transplant with ECMO is a viable treatment option, and active participation in physical therapy, including ambulation, may provide a more rapid post-transplantation recovery. This innovative strategy requires further study to fully evaluate potential benefits and risks.

Heliox administration in the pediatric intensive care unit: an evidence-based review.

Objective: To provide a comprehensive, evidence-based review of helium–oxygen gas mixtures (heliox) in the management of pediatric respiratory diseases. Data Source: A thorough, computerized bibliographic search of the preclinical and clinical literature regarding the properties of helium and its application in pediatric respiratory disease states. Data Synthesis: After an overview of the potential benefits and technical aspects of helium–oxygen gas mixtures, the role of heliox is addressed for asthma, aerosolized medication delivery, upper airway obstruction, postextubation stridor, croup, bronchiolitis, and high-frequency ventilation. The available data are objectively classified based on the value of the therapy or intervention as determined by the study design from which the data are obtained. Conclusions: Heliox administration is most effective during conditions involving density-dependent increases in airway resistance, especially when used early in an acute disease process. Any beneficial effect of heliox should become evident in a relatively short period of time. The medical literature supports the use of heliox to relieve respiratory distress, decrease the work of breathing, and improve gas exchange. No adverse effects of heliox have been reported. However, heliox must be administered with vigilance and continuous monitoring to avoid technical complications.

Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary vascular mechanics and cardiac output in a pediatric swine model

OBJECTIVES In a pediatric swine model, the effects of increasing tidal volumes and the subsequent development of pulmonary overdistention on cardiopulmonary interactions were studied. The objective was to test the hypothesis that increasing tidal volumes adversely affect pulmonary vascular mechanics and cardiac output. An additional goal was to determine whether the effects of pulmonary overdistention are dependent on delivered tidal volume and/or positive end-expiratory pressure (PEEP, end-expiratory lung volume). DESIGN Prospective, randomized, controlled laboratory trial. SETTING University research laboratory. SUBJECTS Eleven 4- to 6-wk-old swine, weighing 8 to 12 kg. INTERVENTIONS Piglets with normal lungs were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. MEASUREMENTS AND MAIN RESULTS The swine were ventilated and data were collected with delivered tidal volumes of 10, 15, 20, and 25 mL/kg and PEEP settings of 5 and 10 cm H2O in a random order. Pulmonary overdistention was defined as a decrease in dynamic compliance of > or =20% when compared with a compliance measured at a baseline tidal volume of 10 mL/kg. At this baseline tidal volume, airway pressure-volume curves did not demonstrate pulmonary overdistention. Tidal volumes and airway pressures were measured by a pneumotachometer and the Pediatric Pulmonary Function Workstation. Inspiratory time (0.75 sec), FIO2 (0.3), and minute ventilation were held constant. We evaluated the pulmonary vascular and cardiac effects of the various tidal volume and PEEP settings by measuring pulmonary vascular resistance, pulmonary characteristic impedance, and cardiac output. When compared with a tidal volume of 10 mL/kg, a tidal volume of 20 mL/kg resulted in a significant decrease in dynamic compliance from 10.5 +/- 0.9 to 8.4 +/- 0.6 mL/cm H2O (p = .02) at a constant PEEP of 5 cm H2O. The decrease in dynamic compliance of 20% indicated the presence of pulmonary overdistention by definition. As the tidal volume was increased from 10 to 20 mL/kg, pulmonary vascular resistance (1351 +/- 94 vs. 2266 +/- 233 dyne x sec/cm5; p = .004) and characteristic impedance (167 +/- 12 vs. 219 +/- 22 dyne x sec/cm5; p = .02) significantly increased, while cardiac output significantly decreased (951 +/- 61 vs. 708 +/- 48 mL/min; p = .001). Each of these effects of pulmonary overdistention were further magnified when the tidal volume was increased to 25 mL/kg. The tidal volume-induced alterations in pulmonary vascular mechanics, characteristic impedance, and cardiac output occurred to a greater degree when the PEEP was increased to 10 cm H2O. Pulmonary vascular resistance and characteristic impedance were significantly increased and cardiac output significantly decreased for all tidal volumes studied at a PEEP of 10 cm H2O as compared with 5 cm H2O. CONCLUSIONS Increasing tidal volumes, increasing PEEP levels, and the development of pulmonary overdistention had detrimental effects on the cardiovascular system by increasing pulmonary vascular resistance and characteristic impedance while significantly decreasing cardiac output. Delivered tidal volumes of >15 mL/kg should be utilized cautiously. Careful monitoring of respiratory mechanics and cardiac function, especially in neonatal and pediatric patients, is warranted.