Rapid Improvement In Oxygenation Research Articles

Rapid Clinical Recovery from Critical COVID-19 Pneumonia with Vasoactive Intestinal Peptide Treatment

IntroductionRLF-100 (Aviptadil), a synthetic form of human Vasoactive Intestinal Peptide (VIP), is in clinical trials for treatment of critical COVID-19 pneumonia with respiratory failure. VIP was shown to protect the lung against a broad array of injuries by binding to the VPAC1 receptor of alveolar type II (ATII) cells, the cells that SARS-CoV-2 binds to. The role of RLF-100 in treating lung transplant patients with COVID-19 pneumonia is unknown.Case ReportA 54 year old man with double lung transplant presented with headache, fever and productive cough. COVID-19 infection was confirmed by positive RT-PCR of nasopharyngeal swab. The patient required only supportive care for three days and was discharged home. Two weeks later he presented with worsening dyspnea, fever and severe hypoxemia requiring high flow O2 and ICU admission. Chest CT showed diffuse bilateral consolidations. He had markedly elevated inflammatory markers. He was treated with dexamethasone and tocilizumab without improvement. He was not a candidate for Remdesivir due to chronic kidney disease. Convalescent plasma was not available. Pro-BNP level was normal; echocardiogram showed preserved biventricular function. He received Aviptadil, a total of three doses, per an open label access under an emergency use approved by US FDA. Rapid improvement in oxygenation and radiologic findings were noticed. No adverse effects were recorded. The patient was transferred out of the ICU 24 hours following the third dose and discharged home on room air 15 days later.SummaryWe report a case of lung transplant recipient with critical COVID-19 pneumonia treated with RLF-100 chieving rapid clinical and radiologic improvement. This is consistent with that VIP protects ATII cells, ameliorating the inflammation and improving oxygenation in critical COVID-19 pneumonia. A randomized prospective trial is underway to evaluate the efficacy of RLF-100 in reducing mortality and improving oxygenation in patients with critical COVID-19 pneumonia.

Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome.

Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model. Preclinical study. Research laboratory. Anesthetized pigs. In vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation. Mass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups. Breath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.

Venoarterial extracorporeal membrane oxygenation in cardiogenic shock: indications, mode of operation, and current evidence

Temporary circulatory support (TCS) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a salvage therapy for patients with refractory cardiogenic shock. This article provides an overview of VA-ECMO principles, indications, management, complications, and discusses the results of recent case series and trials. VA-ECMO is utilized as a bridge to 'decision' that includes weaning after cardiac function recovery, transplantation, long-term mechanical circulatory support, and withdrawal in case of futility. VA-ECMO is considered the first-line TCS as it allows rapid improvement in oxygenation, is less expensive, and is also suitable for patients with biventricular failure. Combining Impella (Abiomed, Danvers, MA, USA) or intra-aortic balloon pump support with VA-ECMO might decrease left ventricular pressure and improve outcomes. Massive pulmonary embolism, sepsis-associated cardiomyopathy, and refractory cardiac arrest are among emerging indications for TCS. TCS have become the cornerstone of the management of patients with cardiogenic shock, although the evidence supporting their efficacy is limited. VA-ECMO is considered the first-line option, with a growing number of accepted and emerging indications. Randomized clinical trials are now needed to determine the place VA-ECMO in cardiogenic shock treatment strategies.

Combined-modality therapy for pulmonary alveolar proteinosis in a remote setting: a case report

BackgroundPulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of phospholipoproteinaceous material in the alveoli. The presentation is nonspecific but typically includes dyspnea; the spectrum of disease includes rapidly progressive hypoxic respiratory failure. Whole lung lavage (WLL) is the treatment of choice in symptomatic PAP, but transient worsening of oxygenation sometimes requires salvage modalities of support such as extracorporeal membrane oxygenation (ECMO). Granulocyte macrophage colony-stimulating factor (GM-CSF) plays a role in the pathophysiology of PAP. We highlight a case of severe PAP treated with exogenous GM-CSF and sequential lobar lavage due to the unavailability of salvage methods of oxygenation.Case presentationA 36 year old female was admitted with fevers, chills, and progressive dyspnea. On presentation she was tachypneic, tachycardic, and hypoxemic; labs revealed leukocytosis and lactic acidosis. Chest CT identified diffuse ground glass opacities in a ‘crazy-paving’ pattern. Following intubation due to impending respiratory failure, bronchoscopy with bronchoalveolar lavage was performed. The lavage return stained positive with Periodic Acid Schiff, confirming the diagnosis of PAP. Continued deterioration necessitated treatment; however, at this geographically remote center without ECMO services WLL was judged to carry significant risk. Nebulized GM-CSF was administered without significant improvement. Subcutaneous GM-CSF was administered and isolated subsegmental lavages of the bilateral upper lobes were performed, with rapid improvement in oxygenation. Additional sequential lobar lavage and continued GM-CSF therapy as an outpatient resulted in complete resolution of oxygen requirement and return to normal pulmonary physiology.ConclusionsThe autoimmune form of PAP is the most common, indicating that therapy with GM-CSF may play an important role for many patients. Treatment with WLL may be impractical in some clinical settings due to the expertise and salvage modalities required. Sequential lobar lavage requires less specialized expertise and may incur less risk of refractory hypoxemia. We posit that this combined-modality therapy is ideally suited to geographically-remote centers such as our own.

Mechanical circulatory devices in acute heart failure.

Temporary circulatory support (TCS) with short-term mechanical circulatory support (MCS) devices is increasingly used as a salvage therapy for patients with refractory cardiogenic shock. This article provides an overview of current devices, their indications and management, and discusses results of recent case series and trials. Percutaneous active MCS devices (Impella, TandemHeart…) and venoarterial extracorporeal membrane oxygenation (VA-ECMO) are utilized as a bridge to 'decision' that includes weaning after cardiac function recovery, transplantation, long-term MCS and withdrawal in case of futility. VA-ECMO is considered the first-line TCS since it allows rapid improvement in oxygenation, is less expensive, and is also suitable for patients with biventricular failure. Combining Impella or intra-aortic balloon pump support with ECMO might decrease left ventricular pressure and improve outcomes. Sepsis-associated cardiomyopathy, massive pulmonary embolism, arrhythmic storm and Takotsubo-like cardiomyopathy are among emerging indications for TCS. TCS have become the cornerstone of the management of patients with cardiogenic shock, although the evidence supporting their efficacy is limited. VA-ECMO is considered the first-line option, with a growing number of accepted and emerging indications. Randomized clinical trials are now needed to determine the respective place of different MCS devices in cardiogenic shock treatment strategies.

Comparison between the effect of heated and humidified high-flow nasal oxygen and conventional oxygen during acute hypoxemic respiratory failure

BackgroundHypoxemia is the most serious threat to organ function. Therefore, the goal is to reverse tissue hypoxia. The aim of this study was to compare heated and humidified high-flow nasal cannula (HFNC) with conventional low-flow nasal cannula (LFNC) oxygen therapy in acute hypoxemic respiratory failure (RF).Patients and methodsThis prospective study was conducted on 60 patients with acute hypoxemic RF. Patients were randomly classified into two groups. Group I received LFNC oxygen therapy. Group II received heated humidified HFNC oxygen therapy. Comparison between the two groups was made using dyspnea scales, heart rate, respiratory rate, and oxygenation status.ResultsThere were no statistically significant differences as regards age, sex, smoking status, causes of RF, and presence of comorbidities between the two groups. There was no statistically significant difference in the modified Borg scale and visual analog scale (VAS) score between the two groups at baseline (P>0.05). After 24 h, the HFNC group had a significant decrease in these scores (P<0.05).Respiratory rate and heart rate significantly decreased, whereas arterial oxygen saturation and tension increased significantly in the HFNC group compared with the conventional LFNC group (P<0.05).Only one patient in the HFNC group versus three patients in the LFNC group required mechanical ventilation. Two patients experienced nasal discomfort in the HFNC group versus five patients in the LFNC group.ConclusionTreatment of acute hypoxemic RF with HFNC was associated with better and rapid improvement in oxygenation when compared with LFNC, with fewer side effects, better convenience, and lesser need for mechanical ventilation.

Effect of inhaled nitric oxide on oxygen therapy, mechanical ventilation, and hypoxic respiratory failure.

To assess the role of inhaled nitric oxide (iNO) in reducing the need for oxygen therapy, decreasing time on mechanical ventilatory support, and attenuating probability of hypoxic respiratory failure severity progression, we reviewed published reports of phase III iNO studies in neonates with hypoxic respiratory failure and pulmonary hypertension, as well as a novel post-hoc analysis of data from the Clinical Inhaled Nitric Oxide Research Group Initiative (CINRGI) study population not been previously reported. The post-hoc analysis of the CINRGI study showed that iNO shortens the duration of oxygen therapy versus placebo (17 vs. 34 days; P<0.05); the CINRGI retrospective analysis by Konduri et al. showed earlier administration of iNO (oxygenation index [OI] 15-25) yielded a 48% relative reduction vs. placebo in number of patients who progressed to OI≥30 (16.7% vs. 32.2%; P=0.002). Golombek and Young's pooled analysis of phase III studies showed a rapid improvement in oxygenation after initiation of iNO therapy versus controls in each study, and a significant reduction in median ventilation duration (11 vs. 14 days; P=0.003). A study by Gonzalez et al. revealed that earlier iNO administration in infants with mild to moderate hypoxic respiratory failure (OI 10-30) resulted in a decreased duration of oxygen therapy versus placebo (11.5 vs. 18.0 days; P<0.03) and reduced the probability of developing severe hypoxic respiratory failure.

Surfactant Therapy for Early Onset Pneumonia in Late Preterm and Term Neonates Needing Mechanical Ventilation.

Pathophysiology of pneumonia involves leakage of plasma proteins into the airways and accumulation of cytokines within the lung. Several in vitro and in vivo studies have demonstrated that this proteinaceous material and lung inflammation inhibit surfactant function. To evaluate whether exogenous surfactant therapy improves oxygenation and gas exchange in late preterm and term neonates with early onset pneumonia and respiratory failure. This prospective interventional cohort study was conducted at a tertiary care neonatal unit. Twenty four late preterm and term neonates with early onset pneumonia requiring mechanical ventilation for respiratory failure were included and received surfactant therapy. Oxygenation index, arterial/alveolar PO2 (a/A ratio), mean airway pressure and fraction of inspired oxygen were calculated from arterial blood gases obtained before and after surfactant therapy. Wilcoxon signed rank sum test was used for assessment of change in oxygenation variables 12 hours after surfactant therapy. Data regarding clinical outcomes and complications were collected and analysed. Just over half (54.2%) of the study neonates were of term gestation. After surfactant therapy, the median Oxygenation Index (OI) decreased from 11.15 to 3.7 at one hour and the change was sustained and significant at 12 hours (p<0.05). The median a/A PO2 ratio improved from 0.09 to 0.3 within one hour of surfactant replacement and the improvement was significant at 12 hours (p<0.01). Twenty two neonates (92%) survived to discharge. Median duration of hospital stay was 15 days. Significant and rapid improvement in oxygenation in late preterm and term neonates with early onset pneumonia was seen after surfactant therapy, which is sustained for a longer period. There could be a substantial role for the use of surfactant in early onset pneumonia, although larger controlled trials are needed before definite recommendations can be made.

Use of High-Frequency Ventilation in the Pediatric Intensive Care Unit.

Objective To evaluate the clinical characteristics, ventilator settings, and gas exchange indices of patients placed on high-frequency percussive ventilation (HFPV) and high-frequency oscillatory ventilation (HFOV). Methods Retrospective observation of all consecutive patients aged 0 to 18 years with acute respiratory failure managed with high-frequency ventilation from the institution's introduction of HFPV on May 1, 2012, until July 10, 2013. Measurements and Main Results Twenty-seven patients underwent HFPV as a first mode of high-frequency ventilation and 16 patients underwent HFOV first. HFPV was used more frequently in patients with acute respiratory illnesses (p < 0.01), lower Pediatric Index of Mortality 2 scores (rank-sum p < 0.04), higher Spo 2/Fio 2 (SF) ratios (p < 0.01), and lower oxygen saturation indices (p < 0.01). HFPV patients showed increased SF ratios (p < 0.01) and decreased Paco 2 levels (p = 0.02) 6 hours after initiation, and HFOV patients showed no significant differences. Peak inspiratory pressures (HFPV) and mean airway pressures (HFOV) remained at or below 30 cm H2O at each time point. HFPV and HFOV patients had an average of 2.8 and 2.9 mode changes, respectively. Mortality was 15% in the HFPV group and 50% in the HFOV group. Conclusions HFPV is associated with rapid improvement in oxygenation and ventilation at acceptable airway pressures in patients with acute respiratory failure of various etiologies, primarily for those with difficulties of ventilation or secretion management. In our institution, HFOV appears to be initiated first in children with higher severity of illness.

Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is characterized by severe worsening dyspnea of unknown etiology and high mortality without effective treatment. Recently, direct hemoperfusion with polymyxin B (PMX)-immobilized fiber cartridge (PMX-DHP) has been reported to improve pulmonary oxygenation and survival in patients with AE-IPF although its mechanism of action remains unknown. To gain insights into the pathobiology of AE-IPF through the beneficial effects of PMX-DHP, we analyzed the profile of cytokines adsorbed onto PMX-fibers used in 9 AE-IPF patients. In addition, the sera of these AE-IPF patients collected immediately before and after PMX-DHP, 9 stable IPF patients and 8 healthy individuals were also analyzed. The serum levels of cytokines including IL-9, IL-12, IL-17, PDGF and VEGF were significantly decreased immediately after PMX-DHP (P<0.02), and VEGF and IL-12 were most prominently reduced. In addition to PDGF and VEGF, IL-1β, IL-1ra, IL-8, IL-23, FGF basic, GM-CSF, IP-10, RANTES and TGF-β were eluted from used PMX-fibers. Interestingly, improved pulmonary oxygenation after PMX-DHP was correlated well with the quantities of eluted VEGF. These results suggest that adsorption of proinflammatory, profibrotic and proangiogenic cytokines onto PMX-fibers is one of the mechanisms of action of PMX-DHP in AE-IPF. Notably, removal of VEGF by PMX-DHP may contribute to the rapid improvement in oxygenation by suppressing vascular permeability in the lung.

Thrombolytic Therapy in a Patient With Suspected Pulmonary Embolism Despite a Negative Computed Tomography Pulmonary Angiogram

We report a case of a 62-year-old male who presented to our intensive care unit with hypoxemia 6 hours after retinal surgery. He had a negative computed tomography (CT) pulmonary angiogram, but an emergency echocardiogram revealed the McConnell sign. He was thrombolysed and had rapid improvement in oxygenation and hemodynamics. Thrombolysis in hemodynamically unstable pulmonary embolism is not controversial, but most algorithms require confirmation of the diagnosis. Our patient had a negative CT pulmonary angiogram but was thrombolysed based on the clinical picture. Autopsy confirmed the diagnosis of multiple pulmonary emboli and unexpectedly discovered a patent foramen ovale that explained paradoxical embolism to the brain.

Early discontinuation of intravenous prostaglandin E1 after balloon atrial septostomy is associated with an increased risk of rebound hypoxemia

A comparison of the effects of early (<2 h) and late (>or=2 h) discontinuation of prostaglandin E1 (PGE1), on systemic oxygenation following a successful balloon atrial septostomy (BAS), in neonates with confirmed diagnosis of d-transposition of the great arteries (d-TGA). Neonates with a postnatal diagnosis of d-TGA who were admitted to a quaternary neonatal intensive care unit between January 1999 and December 2004 were identified from the local database. The effects of time of discontinuation of PGE1 on oxygen saturations, oxygen requirement, need for reinstitution of prostaglandin infusion and postoperative stability were analyzed. Sixty neonates with a diagnosis of d-TGA were identified, 45 of whom had a BAS performed. Of these, 25 cases had early (<2 h) discontinuation of PGE1 whereas in the remaining 20 discontinuation was late (>or=2 h). PGE1 infusion was recommenced in 20 neonates (20/45 (44%)) after a successful BAS due to rebound hypoxemia. Of these, there was a threefold increase in the need for reinstitution of prostaglandin in the early compared to late discontinuation group (16/25 (64%) vs 4/20 (20%), P<0.006). There was no difference in postoperative cardiorespiratory stability. Early discontinuation of intravenous PGE1 following BAS was associated with an increased risk of rebound hypoxemia, necessitating the recommencement of PGE1. We speculate the rapid improvement in oxygenation on reinstitution of PGE1 is secondary to pulmonary vasodilation and improved pulmonary blood flow. We propose a more cautious and graded approach to discontinuation of PGE1 based on illness severity and the magnitude and duration of hypoxemia at presentation.

Sivelestat relieves respiratory distress refractory to dexamethasone in all‐trans retinoic acid syndrome: a report of two cases

Kawasaki K, Akaike H, Miyauchi A, Ouchi K. Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome: a report of two cases.Treatment with all-trans retinoic acid (ATRA) improves the prognosis of patients with acute promyelocytic leukemia (APL), but ATRA syndrome may occur as a possible fatal side effect, especially in cases refractory to medication or involving pulmonary hemorrhage. We describe two patients with APL who suffered from intracranial hemorrhage. The first patient was a 16-yr-old girl who was treated with ATRA and then developed respiratory distress refractory to treatment with dexamethasone combined with anthracycline-cytarabine cytoreduction therapy. Treatment with Sivelestat, a small molecule inhibitor of neutrophil elastase, achieved rapid improvement in oxygenation and chest radiograph findings, and the patient has been in complete remission for 24 months. The second patient was a 10-yr-old boy in whom pulmonary hemorrhage developed following administration of ATRA, dexamethasone and cytoreduction therapy. Aspiration and administration of Sivelestat improved oxygenation and he remained stable. Hematological improvement was also achieved, but the patient died of brain dysfunction because of cerebral edema accompanied by intracranial bleeding. The two cases suggest that Sivelestat may be effective as an additional agent in the treatment of refractory ATRA syndrome, and, therefore, prospective randomized studies of treatment protocols are warranted.

Effect of corticosteroids on adult varicella pneumonia: Cohort study and literature review

Varicella pneumonia (VP) is a serious entity associated with morbidity and mortality. There have been sporadic reports using corticosteroids in life-threatening VP. We report a case series of VP to examine the outcome and the effect of corticosteroid use. A retrospective chart review was conducted on all adult patients admitted to a tertiary care hospital with VP during a 14-year period. We documented oxygenation (SpO2, PaO2/FIO2) on admission and after 48 h, whether the patients were admitted to an intensive care unit (ICU), the use of mechanical ventilation, ICU and hospital length of stay (LOS) and patient outcome. We compared those patients who received corticosteroids with those who did not. We identified 19 patients with VP. Ten received corticosteroids, in addition to antiviral and supportive treatment. Patients who received corticosteroids were significantly more hypoxaemic on admission and all were admitted to ICU with seven of them intubated. Only two of the nine in non-steroid group were intubated. Despite their greater severity, the corticosteroid group showed a much more rapid improvement in oxygenation and a trend towards shorter duration of mechanical ventilation. The duration of ICU and hospital LOS were not significantly different. All patients survived. Corticosteroids in severe VP accelerate the physiological recovery and may shorten the duration of mechanical ventilation.

Overview of Surfactant Replacement Trials

Clinical trials have evaluated the overall efficacy of surfactant therapy, as well as the relative efficacy of different surfactant preparations, the optimal timing of administration and the optimal dosage. Surfactant therapy leads to significant clinical improvement in infants at risk for, or having, respiratory distress syndrome (RDS). Clinical trials that compared the effects of synthetic or animal-derived surfactant preparations to placebo or no therapy demonstrate that surfactant therapy lead to rapid improvement in oxygenation, decreased ventilator support, decreased risk of pneumothorax, and mortality. Earlier treatment, prophylactic treatment of infants at high risk of developing RDS, and selective re-treatment leads to improved clinical outcome as well. Currently available animal-derived surfactants are superior to non-protein-containing synthetic surfactants. Ongoing evaluation will determine if important differences in animal-derived products are noted. Future trials will evaluate third-generation surfactant products and further refine what constitutes optimal use of surfactant.

Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial

Non-invasive pressure support ventilation (NIPSV) is an effective treatment for acute respiratory failure in patients with chronic obstructive pulmonary disease. We assessed the efficacy of this therapy in acute cardiogenic pulmonary oedema in a randomised comparison with conventional oxygen therapy. 40 patients were randomly assigned conventional oxygen therapy or NIPSV supplied by a standard ventilator through a face mask, with adjustment of tidal volume and pressure support in addition to a positive end-expiratory pressure of 5 cm water. Physiological measurements were obtained in the first 2 h and at 3 h, 4 h, and 10 h. The main endpoints were intubation rate and resolution time. Analyses were by intention to treat. Three patients were withdrawn on the basis of clinical and chest radiography results. Endotracheal intubation was required in one (5%) of 19 patients assigned NIPSV and in six (33%) of 18 assigned conventional oxygen therapy (p=0.037). Resolution time (defined as a clinical improvement with oxygen saturation of 96% or more and respiratory rate less than 30 breaths/min) was significantly shorter in the NIPSV group (median 30 [IQR 15-53] vs 105 [50-230] min, p=0.002). NIPSV led to a rapid improvement in oxygenation in the first 2 h. There were no differences in hospital length of stay or mortality. In this study of acute cardiogenic pulmonary oedema, NIPSV was superior to conventional oxygen therapy. Further studies should compare NIPSV with continuous positive airway pressure.

Surfactant supplementation in respiratory syncytial virus bronchiolitis

Infants with respiratory syncytial virus (RSV) bronchiolitis are deficient in surfactant, both in quantity and ability to reduce surface tension. Evidence also suggests surfactant has a role in maintaining the patency of conducting airways which has implications for RSV bronchiolitis. A randomized, controlled trial was undertaken to assess the effects of exogenous surfactant supplementation to RSV positive infants on pulmonary mechanics, indices of gas exchange, and the phospholipid composition of bronchoalveolar lavage fluid (BALF). Nineteen ventilated infants (median corrected age 4 weeks) received either two doses of surfactant (Survanta, 100 mg kg−1) within 24 and 48 h of mechanical ventilation (n = 9), or air placebo (n = 10). Lung mechanics were measured using the single breath occlusion technique, before dose, and at 1, 2 and 6 h after each dose. BALF were taken before the first dose, and 24 h after the second. Phospholipid profiles were measured by electrospray ionisation mass spectrometry. Statistical analysis employed 2-way, repeated measures ANOVA, with post hoc Bonferroni adjusted t-tests comparing time point 0 h (before treatment) and 30 h (6 h after second treatment). Infants were well matched in terms of age, prematurity, chronic lung disease and severity of lung disease at enrolment. Static lung compliance and resistance of infants in the placebo but not in the surfactant-treated group became progressively worse over the first 30 h following enrolment (Table 28). Surfactant-treated infants showed a more rapid improvement in oxygenation and ventilation indices and alveolar-arterial gradient over the first 60 h of mechanical ventilation. Surfactant status was assessed from the concentration ratio in BALF of the disaturated phospholipid species dipalmitoylphosphatidylcholine to that of the monounsaturated species palmitoyloleoylphosphatidylcholine. This ratio correlated with both lung compliance (r = 0.53, P = 0.02) and resistance (r = –0.50, P = 0.03), and over time increased in the treated group and declined in placebo infants. These data suggest that functional surfactant has a role in maintaining small airway patency in RSV infected infants and supplementation has the potential to reduce length of ventilation and barotrauma.

Improved oxygenation after discontinuing neuromuscular blockade.

Objective:To evaluate the effects of prolonged neuromuscular blockade (NMB) on oxygenation and duration of mechanical ventilation in children with respiratory failure.Design:Retrospective case control study.Setting:The pediatric intensive care unit (PICU) of a tertiary university hospital.Patients:All children (n=68) in the PICU ventilated for pulmonary parenchymal disease for 3 days or longer over a 412 year period.Interventions:None.Measurements and results:Diagnoses, pediatric risk of mortality scoring, indications for, and duration of, mechanical ventilation and neuromuscular blockade, and blood gas data with corresponding ventilator parameters were extracted from the medical records. Twenty-eight patients received NMB at the initiation of mechanical ventilation and this was continued for 72 h or longer. Cessation of NMB was associated with a significant improvement in ventilator parameters and oxygenation index. The subset of children with respiratory syncytial virus disease (RSV) receiving prolonged NMB had longer ventilator courses compared to those in whom NMB was not used, despite similar demographics, severity of illness and oxygenation impairment.Conclusions:Stopping NMB is associated with a rapid improvement in oxygenation and prolonged use of NMB in children with RSV is associated with a protracted ventilatory course.Definition:Oxygenation index (OI)*: Mean Airway Pressure ×FiO2×100/PaO2 * Higher scores represent deterioration in oxygenation

Calf's lung surfactant extract in acute hypoxemic respiratory failure in children

Open-label trial of the safety and short-term efficacy of calf's lung surfactant in pediatric respiratory failure. Multi-institutional, uncontrolled, observational trial. Six pediatric intensive care units of tertiary medical centers. Twenty-nine children with acute hypoxemic respiratory failure, characterized by diffuse, bilateral, pulmonary infiltrates, need for ventilator support, and an oxygenation index of > or = 7. Up to four doses of intratracheal surfactant (80 mL/m2). Ventilator parameters, arterial blood gases, and derived oxygenation and ventilation indices were recorded before, and at intervals after, surfactant administration. Complications and outcome measures were also noted. There was immediate improvement in oxygenation and moderation of ventilator support associated with surfactant administration in 24 of 29 patients. A modest but statistically insignificant effect was seen with subsequent doses. The only complications occurred in three patients who developed airleaks, two of which were coincident with surfactant administration. The overall mortality rate was 14%, which compares favorably with other published series. Administration of calf's lung surfactant appears to be safe and is associated with rapid improvement in oxygenation and moderation of ventilator support in children with acute hypoxemic respiratory failure. These results set the stage for a randomized, controlled study.

Randomised clinical trial of two treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome.

To compare treatment regimens of two widely used natural surfactant preparations Curosurf and Survanta in respiratory distress syndrome (RDS). The effects of the two treatment regimens on gas exchange, ventilatory requirements, and 28 day outcome in infants with RDS were compared. Seventy five preterm infants (birth weight 700-1500 g) with RDS requiring artificial ventilation with an FIO2 of > or = 0.4, were randomly selected at 1-24 hours of age. One group received an initial dose of Curosurf (200 mg/kg); the other group Survanta (100 mg/kg). Patients who remained dependent on artificial ventilation with an FIO2 of > or = 0.3 received up to two additional doses of Curosurf (each of 100 mg/kg) after 12 and 24 hours or up to three additional doses of Survanta (each of 100 mg/kg) between six and 48 hours after the initial dose. There was a rapid improvement in oxygenation and ventilatory requirements were reduced in both groups. However, infants treated with Curosurf had a higher arterial:alveolar oxygen tension ratio and required a lower peak inspiratory pressure and mean airway pressure at several time points within 24 hours of randomisation (p < 0.05-0.001). The incidences of pneumothorax in the Curosurf and Survanta groups were 6% and 12.5%, respectively; the corresponding figures for grades 3-4 intracerebral haemorrhage were 3% and 12.5%, respectively. Mortality was 3% in the Curosurf group and 12.5% in the Survanta group. However, these differences did not reach significance. The Curosurf treatment regimen resulted in a more rapid improvement in oxygenation than Survanta and reduced ventilatory requirements up to 24 hours after start of treatment. This was associated with a trend towards reduced incidence of serious pulmonary and non-pulmonary complications.