Effect of tidal volume in children with acute hypoxemic respiratory failure

Objectives  To determine if tidal volume (V _T) between 6 and 10 ml/kg body weight using pressure control ventilation affects outcome for children with acute hypoxemic respiratory failure (AHRF) or acute lung injury (ALI). To validate lung injury severity markers such as oxygenation index (OI), PaO₂/FiO₂ (PF) ratio, and lung injury score (LIS). Design  Retrospective, January 2000–July 2007. Setting  Tertiary care, 20-bed PICU. Patients  Three hundred and ninety-eight endotracheally intubated and mechanically ventilated children with PF ratio <300. Outcomes were mortality and 28-day ventilator free days. Measurements and main results  Three hundred and ninety-eight children met study criteria, with 20% mortality. 192 children had ALI. Using >90% pressure control ventilation, 85% of patients achieved V _T less than 10 ml/kg. Median V _T was not significantly different between survivors and non-survivors during the first 3 days of mechanical ventilation. After controlling for diagnostic category, age, delta P (PIP-PEEP), PEEP, and severity of lung disease, V _T was not associated with mortality (P > 0.1), but higher V _T at baseline and on day 1 of mechanical ventilation was associated with more ventilator free days (P < 0.05). This was particularly seen in patients with better respiratory system compliance [Crs > 0.5 ml/cmH₂0/kg, OR = 0.70 (0.52, 0.95)]. OI, PF ratio, and LIS were all associated with mortality (P < 0.05). Conclusions  When ventilating children using lung protective strategies with pressure control ventilation, observed V _T is between 6 and 10 ml/kg and is not associated with increased mortality. Moreover, higher V _T within this range is associated with more ventilator free days, particularly for patients with less severe disease. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Inability to predict outcome of acute respiratory distress syndrome in children when using high frequency oscillation

Objective To (a) describe the experience with high-frequency oscillation (HFO) in children with acute respiratory distress syndrome (ARDS) unresponsive to conventional ventilation; (b) compare observed survival to that predicted by pediatric mortality scores and (c) determine if oxygenation index changes during HFO can predict survival.Design Retrospective, observational study.Setting A university hospital pediatric intensive care unit.Patients Nineteen children with ARDS (PaO₂/FIO₂<200) unresponsive to conventional ventilation treated with HFO from January 1995 to September 1996.Interventions None.Measurements and results The following were recorded: demographic, arterial blood gas and ventilator variables at the time points 0, 6, 12 and 24 h after the start of HFO; PRISM in the first 24 h of admission and pediatric respiratory failure and multiple organ system failure scores on the day of starting HFO. The mortality rate was 26% (5/19). The survival was better than predicted by the Pediatric Respiratory Failure score (p<0.01). None of the scores differentiated survivors from non-survivors (p>0.25). There was no significant change in oxygenation index over the first 24 h (p>0.18). Of patients with an initial oxygenation index higher than 20 who did not have at least a 20% reduction in oxygenation index by the time 6 h, 6/9 (67%) survived (sensitivity 75%, specificity 57%).Conclusions Survival in pediatric ARDS patients treated with HFO could not be predicted using several outcome scores or the oxygenation index (in the first 24 h). Survival was significantly better than predicted by the Pediatric Respiratory Failure score. A prospective randomized controlled trial of HFO in ARDS is warranted.     

Timing of recovery of lung function after severe hypoxemic respiratory failure in children

Objective: To describe the timing of recovery of lung function after severe acute hypoxemic respiratory failure (AHRF) in children. Design: A serial observational follow-up study of clinical and lung function measurements up to 53 months after acute illness. Setting: University pediatric intensive care unit in a national children's hospital. Patients: Five critically ill children aged 5–14 years. Interventions: None Results: Clinical recovery: each patient required a 3–5 month convalescence before being able to attend full-time school because of lethargy and dyspnea. All patients developed wheeze 3–12 months after illness and four received long-term bronchodilator therapy. Lung function recovery: for both the forced vital capacity (FVC) and forced vital capacity in the first second (FEV₁) four patients had abnormally low values, regaining only 60–70 % of predicted values for their height and sex, and all of this improvement had occurred by 6–12 months after illness. Beyond this interval, patients remained on their same FVC and FEV₁ centile. FEV₁/FVC ratios were consistently within the normal range, indicating a predominantly restrictive defect. Changes in peak expiratory flow exhibited a time course of improvement similar to the other lung function tests. Conclusion: In children, pulmonary recovery after severe AHRF may occur for 6–12 months. A 1-year follow-up could offer a rational single point for assessment of outcome and long-term counselling of child and parents. Received: 10 November 1997 Accepted: 20 January 1998     

Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19

AimNoninvasive ventilation (NIV) is known to reduce intubation in patients with acute hypoxemic respiratory failure (AHRF). We aimed to assess the outcomes of NIV application in COVID-19 patients with AHRF.Materials & methodsIn this retrospective cohort study, patients with confirmed diagnosis of COVID-19 and AHRF receiving NIV in general wards were recruited from two university-affiliated hospitals. Demographic, clinical, and laboratory data were recorded at admission. The failure of NIV was defined as intubation or death during the hospital stay.ResultsBetween April 8 and June 10, 2020, 61 patients were enrolled into the final cohort. NIV was successful in 44 out of 61 patients (72.1%), 17 patients who failed NIV therapy were intubated, and among them 15 died. Overall mortality rate was 24.6%. Patients who failed NIV were older, and had higher respiratory rate, PaCO₂, D-dimer levels before NIV and higher minute ventilation and ventilatory ratio on the 1-st day of NIV. No healthcare workers were infected with SARS-CoV-2 during the study period.ConclusionsNIV is feasible in patients with COVID-19 and AHRF outside the intensive care unit, and it can be considered as a valuable option for the management of AHRF in these patients.     

Oxygen tolerance in patients with acute respiratory failure

Objective: To search for a threshold of pulmonary oxygen toxicity in patients with acute respiratory failure. Design: Retrospective study over a 10-year period. Setting: Three intensive care units of two university hospitals. Patients and participants: Seventy-four patients with acute respiratory failure ventilated continuously with a FIO₂ L 0.9 for at least 48 h were selected. Interventions: Information regarding status, scoring, diagnosis and therapeutic interventions upon admission and ICU course were extracted from the patients' charts. Measurements and results: We found that total exposure [mean (standard error of the mean) ] to a FIO₂ of 0.9 (TE 90) or more was 5.6 (1.1) days in the 17 survivors (S) versus 5.9 (0.5) days in the 57 non-survivors (D) (NS). Total exposure time to a FIO₂ more than 0.5 (TE 50) was 16.5 (2.6) days in S and 11.2 (1) days in D (p < 0.05). The PaO₂/FIO₂ ratio became significantly higher in S only 5 days after beginning FIO₂ of 0.9 or more. Hypoxemia was not frequent at the time of death, whereas in 70 % of the non-survivors there were at least three organ failures in the last 48 h. In univariate analysis, the duration of exposure to FIO₂ of 0.9 or more was not different in survivors and non-survivors, and the average total duration of exposure to FIO₂ of more than 0.5 was even longer in survivors. In multivariate analysis, exposure shorter than 10 days to FIO₂ more than 0.5 and exposure longer than 4 days to a FIO₂ of 0.9 or more were significantly associated with death. However, despite a larger exposure to a FIO₂ of 0.9 or more during the last 5 years of the study, the trend moved towards a higher survival rate during this period compared with the first 5 years of the study. Conclusions: Thus, our data provide circumstantial evidence that the lungs of patients with acute respiratory failure might exhibit some relative resistance to prolonged oxygen exposure. Therefore, it might be worthwhile carrying out a prospective study of different FIO₂ strategies in such patients. Received: 14 February 1997 Accepted: 2 March 1998     

Prognostic value of extravascular lung water index in critically ill children with acute respiratory failure

Purpose

In critically ill adults, a reduction in the extravascular lung water index (EVLWi) decreases time on mechanical ventilation and improves survival. The purpose of this study is to assess the prognostic value of EVLWi in critically ill children with acute respiratory failure and investigate its relationships with PaO₂, PaO₂/FiO₂ ratio, A-aDO₂, oxygenation index (OI), mean airway pressure, cardiac index, pulmonary permeability, and percent fluid overload.

Methods

Twenty-seven children admitted to PICU with acute respiratory failure received volumetric hemodynamic and blood gas monitoring following initial stabilization and every 4?h thereafter, until discharge from PICU or death. All patients are grouped in two categories: nonsurvivors and survivors.

Results

Children with a fatal outcome had higher values of EVLWi on admission to PICU, as well as higher A-aDO₂ and OI, and lower PaO₂ and PaO₂/FIO₂ ratio. After 24?h EVLWi decreased significantly only in survivors. As a survival indicator, EVLWi has good sensitivity and good specificity. Changes in EVLWi, OI, and mean airway pressure had a time-dependent influence on survival that proved significant according to the Cox test. Survivors spent fewer hours on mechanical ventilation. We detected a correlation of EVLWi with percent fluid overload and pulmonary permeability.

Conclusions

Like OI and mean airway pressure, EVLWi on admission to PICU is predictive of survival and of time needed on mechanical ventilation.     

小儿急性低氧性呼吸衰竭呼吸支持相关预后差异及影响因素

目的 探讨26家医院小儿重症监护室(PICU)患者呼吸支持相关的预后之差异及影响因素.方法 多中心前瞻性临床协作研究,研究时间为2005年12月至2006年11月连续12个月,研究对象为29 d至15周岁的PICU患儿.患儿纳入后记录其基本情况、疾病诊断、治疗及预后等数据,汇总后分析不同PICU其患者预后及呼吸治疗的差异.结果 在研究期间,26家PICU共收治危重病例11521例,占PICU收治患者总数的70%,不同单位该比例从14%到98%.26家单位共纳入小儿低氧性呼吸衰竭(AHRF)病例461例,患病率4%,各单位AHRF患病率中位值4.7%(Qr:2.4%～7.1%).AHRF总病死率41.6%,26家PICU病死率中位值39.8%(四分位数间距22%～57%).AHRF病死率在大学附属医院低于非大学附属医院(37%vs.46%,x~2=4.16,P:0.04),经济发达地区低于欠发达地区医院(38%vs.46%,x~2=3.1,P=0.08).结论 我国不同地区及不同类别医院PICU危重病例及AHRF呼吸支持相关的预后存在较大差异.PICU所在医院的学术背景及地区经济发展水平是影响患者预后的两个重要原因.在开展提高PICU的呼吸支持治疗水平和AHRF生存率的干预性研究设计中应予考虑.     

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 Received: 26 January 1996 Accepted: 5 August 1996     

Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors

Introduction

We assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF).

Methods

This is an observational cohort study using data prospectively collected over a three-year period in a medical ICU of a university hospital.

Results

Among 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO₂/FiO₂ >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation.

Conclusions

With intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO₂/FiO₂ > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality.     

Angiotensin-converting enzyme D allele does not influence susceptibility to acute hypoxic respiratory failure in children

Objective  The D allele of the I/D polymorphism in the angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of ARDS in critically ill adults and severity of bronchopulmonary dysplasia in pre-term infants. We hypothesised that the presence of the hypoxia-associated ACE D allele would increase susceptibility to acute hypoxic respiratory failure (AHRF) in a cohort of critically ill children. Design and setting  Single-centre prospective observational cohort study. Patients  Children under 16 years of age requiring admission to a tertiary general PICU. Measurements and results  A total of 216 Caucasian patients were enrolled. Thirty (13.9%) children developed AHRF and 13 were diagnosed with ARDS (6.0%). There was no significant difference in ACE D allele frequency between patient groups with or without AHRF (0.53 vs. 0.54). Conclusions  Variation in ACE activity does not influence the development of paediatric AHRF. This may reflect a different pathogenesis from adult ARDS.     

Application of SOFA score to trauma patients

Objective: To assess the ability of the SOFA score (Sequential Organ Failure Assessment) to describe the evolution of organ dysfunction/failure in trauma patients over time in intensive care units (ICU). Design: Retrospective analysis of a prospectively collected database. Setting: 40 ICUs in 16 countries. Patients: All trauma patients admitted to the ICU in May 1995. Main outcome measures and results: Incidence of dysfunction/failure of different organs during the first 10 days of stay and the relation between the dysfunction, outcome, and length of stay. Included in the SOFA study were 181 trauma patients (140 males and 41 females).The non-survivors were significantly older than the survivors (51 years ± 20 vs 38 ± 16 years, p < 0.05) and had a higher global SOFA score on admission (8 ± 4 vs 4 ± 3, p < 0.05) and throughout the 10-day stay. On admission, the non-survivors had higher scores for respiratory ( > 3 in 47 % of non-survivors vs 17 % of survivors), cardiovascular ( > 3 in 24 % of non-survivors vs 5.7 % of survivors), and neurological systems ( > 4 in 41 % of non-survivors vs 16 % of survivors); although the trend was maintained over the whole study period, the differences were greater during the first 4–5 days. After the first 4 days, only respiratory dysfunction was significantly related to outcome. A higher SOFA score, admission to the ICU from the same hospital, and the presence of infection on admission were the three major variables associated with a longer length of stay in the ICU (additive regression coefficients: 0.85 days for each SOFA point, 4.4 for admission from the same hospital, 7.26 for infection on admission). Conclusions: The SOFA score can reliably describe organ dysfunction/failure in trauma patients. Regular and repeated scoring may be helpful for identifying categories of patients at major risk of prolonged ICU stay or death. Received: 3 March 1998 Accepted: 21 December 1998     

Cephalic versus oronasal mask for noninvasive ventilation in acute hypercapnic respiratory failure

Objective  Compared to oronasal interfaces, a cephalic mask has a larger inner volume, covers the entire anterior surface of the face and limits the risk of deleterious cutaneous side effects during noninvasive ventilation (NIV). The present clinical study aimed to compare the clinical efficacy of a cephalic mask versus an oronasal mask in patients with acute hypercapnic respiratory failure (AHRF). Design and setting  Randomized controlled study in a Respiratory Intermediate Care Unit. Patients  All consecutive patients admitted for AHRF were randomly assigned to receive bilevel NIV either with a cephalic mask (n = 17) or an oronasal mask (n = 17) during the first 48 h. Measurements  The main outcome criterion was the improvement of arterial pH, 24 h after NIV initiation. Secondary criteria included PaCO₂ and physiological parameters. Results  Compared to values at inclusion, pH, PaCO₂, encephalopathy score, respiratory distress score and respiratory frequency improved significantly and similarly with both masks. None of these parameters showed statistically significant differences between the masks at each time point throughout the study period. Mean delivered inspiratory and expiratory pressures were similar in both patient groups. Tolerance of the oronasal mask was improved at 24 h and further. One patient with the cephalic mask suffered from claustrophobia that did not lead to premature study interruption. Conclusions  In spite of its larger inner volume, the cephalic mask has the same clinical efficacy and requires the same ventilatory settings as the oronasal mask during AHRF.     

Continuous arteriovenous haemofiltration and respiratory function in multiple organ systems failure

Objective: To determine what change in respiratory function occurred following prolonged and efficient continuous arteriovenous haemofiltration (CAVH) in a group of patients with multiple organ systems failure (MOSF).Design: A retrospective assessment using patient notes and ICU charts.Setting: The Intensive Care Unit of a large University Teaching Hospital.Patients: All ICU patients satisfying the following criteria: (i) Failure of more than one organ system; (ii) Treatment with CAVH; (iii) Removal of more than 10 l of ultrafiltrate per day; (iv) Continuous haemofiltration for at least 5 days. Thirteen patients satisfied these criteria and 14 episodes of CAVH were analyzed.Measurements: All data were recorded from the patient notes and ICU charts apart from the A-aDO₂ and PaO₂/FiO₂ (PF) ratio which were calculated from available values. A mean of 3.5 different organ systems failed during the period of stay. The mean daily ultrafiltrate volume obtained was 23.7 (SD 0.95) 1 and the mean duration of treatment 9.5 (SD 4.3) days. Significant improvements occurred in the values for the PF ratio and ventilatory modality (p<0.05), and the FiO₂ and A-aDO₂ (p=0.001). The mean PEEP value remained unchanged at 4.8 cmH₂O. Ten of the 13 patients subsequently died (77% mortality).Conclusions: A significant improvement in respiratory function occurred in patients with MOSF who had undergone a prolonged period of intense CAVH. Haemofiltration may therefore be a useful treatment for respiratory failure in this patient group. Unfortunately the overall mortality of the group remained high.     

Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome

Background: Despite intensive research, there are no universally accepted clinical definitions for acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment. However, this definition may not reflect the true prevalence, severity and prognosis of these syndromes. Methods: During a 22-month period, 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [arterial oxygen tension/fractional inspired oxygen (PaO₂/FIO₂≤ 200 mmHg regardless of the level of positive end-expiratory pressure (PEEP), bilateral pulmonary infiltrates, and no evidence of left heart failure] were admitted into the intensive care units (ICU) of the Hospital del Pino, Las Palmas, Spain, and prospectively studied. The diagnosis of ALI and ARDS was made by a PEEP-FIO₂ trial, 24 h after patients met the Consensus inclusion criteria. Patients were classified as having ALI_{–24 h} if the PaO₂/FIO₂ was > 150 mmHg with PEEP = 5 cmH₂O, and ARDS_{–24 h} if the PaO₂ /FIO₂ was ≤ 150 mmHg with PEEP ≥ 5 cmH₂O. Results: Overall mortality was 43 % (24 of 56). However, 24 h after inclusion, PaO₂ response to PEEP 5 cmH₂O allowed the separation of our patients into two different groups: 31 patients met our ALI_{–24 h} criteria (PaO₂/FIO₂ > 150 mmHg) and their mortality was 22.6 %; 25 patients met our ARDS_{–24 h} criteria (PaO₂/FIO₂≤ 150 mmHg) and their mortality was 68 % (p = 0.0016). The differences in the respiratory severity index during the first 24 h of inclusion, PaO₂/FIO₂ ratio at baseline and at 24 h, maximum plateau airway pressure, maximum level of PEEP, and number of organ system failures during the ICU stay were statistically significant. Conclusions: Since the use of PEEP in the American-European Consensus criteria for ARDS is not mandatory, that definition does not reflect the true severity of lung damage and outcome. Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted. Received: 18 April 1999 Final revision received: 30 June 1999 Accepted: 9 July 1999     

Co-morbidity and acute decompensations of COPD requiring non-invasive positive-pressure ventilation

Objective To assess the prevalence and the impact of chronic and/or acute non-respiratory co-morbidity on short and longer-term outcome of non-invasive positive pressure ventilation (NIPPV) in acute decompensations of chronic obstructive pulmonary disease (COPD) with acute hypercapnic respiratory failure (AHRF).Design and setting An observational study in a three-bed respiratory monitoring unit in a respiratory ward of a non-university hospital.Patients We grouped 120 consecutive COPD patients requiring NIPPV for AHRF (pH 7.28±0.05, PaO₂/FIO₂ ratio 192±63, PaCO₂ 78.3±12.3 mmHg) according to whether NIPPV succeeded (n=98) or failed (n=22) in avoiding the need for endotracheal intubation and whether alive (n=77) or dead (n=42) at 6 months.Measurements and results The prevalence of chronic and acute co-morbidity was, respectively, 20% and 41.7%; most of the cases were cardiovascular. In-hospital NIPPV failure was greater in patients with than in those without chronic (33.3% vs. 14.6%) or acute co-morbidity (32% vs. 8.6%). Six-month mortality was worse in patients with than in those without chronic (54.2% vs. 30.5%) or more than one acute co-morbidity (66.7% vs. 30.8%). Multiple regression analysis predicted in-hospital NIPPV failure by acute co-morbidity and forced expiratory volume in 1 s, while death at 6 months was predicted by having more than one acute co-morbidity, non-cardiovascular chronic co-morbidity and Activities of Daily Living score.Conclusions Chronic and acute co-morbidities are common in COPD patients with AHRF needing NIPPV and their presence influences short and longer-term outcome.     

Effects of noninvasive positive pressure ventilatory support in non-COPD patients with acute respiratory insufficiency after early extubation

Objective: To investigate the effects of noninvasive positive pressure ventilation (NPPV) on pulmonary gas exchange, breathing pattern, intrapulmonary shunt fraction, oxygen consumption, and resting energy expenditure in patients with persistent acute respiratory failure but without chronic obstructive pulmonary disease (COPD) after early extubation. Design: Prospective study. Setting: Multidisciplinary intensive care unit of a university hospital. Patients: 15 patients after prolonged mechanical ventilation (> 72 h) with acute respiratory insufficiency after early extubation. Interventions: Criteria for early extubation were arterial oxygen tension (PaO₂) L 40 mm Hg (fractional inspired oxygen 0.21), arterial carbon dioxide tension (PaCO₂) K 55 mm Hg, pH > 7.32, respiratory rate K 40 breaths per min, tidal volume (V_T) L 3 ml/kg, rapid shallow breathing index K 190 and negative inspiratory force L 20 cmH₂O. After extubation, two modes of NPPV were applied [continuous positive airway pressure (CPAP) of 5 cmH₂O and pressure support ventilation (PSV) with 15 cmH₂O pressure support]. Measurements and main results: Oxygenation and ventilatory parameters improved during both modes of NPPV (p < 0.05): increase in PaO₂ of 11 mm Hg during CPAP and 21 mm Hg during PSV; decrease in intrapulmonary shunt fraction of 7 % during CPAP and 12 % during PSV; increase in tidal volume of 1 ml/kg during CPAP and 4 ml/kg during PSV; decrease in respiratory rate 6 breaths/min during CPAP and 9 breaths/min during PSV. Oxygen consumption (15 % during CPAP, 22 % during PSV) and resting energy expenditure (12 % during CPAP, 20 % during PSV) were reduced (p < 0.05). PaCO₂ decreased, whereas minute ventilation and pH increased during PSV (p < 0.05). The median duration of NPPV was 2 days. Two patients had to be reintubated. Conclusions: In non-COPD patients with persistent acute respiratory failure after early extubation, NPPV improved pulmonary gas exchange and breathing pattern, decreased intrapulmonary shunt fraction, and reduced the work of breathing. Received: 14 May 1999 Final revision received: 25 June 1999 Accepted: 6 July 1999     

Changes in left ventricular function in shocked newborns

Objective: To assess whether the change in cardiac output after volume replacement is due to elevation of stroke volume or heart rate and to determine the effect of mechanical ventilation on the hemodynamic situation. Design: Prospective study. Setting: A ten-bed neonatal intensive care unit (level III) at a university hospital. Patients: 15 consecutive newborns with blood pressure below the 10^th percentile related to age and weight. Interventions: Volume replacement with Ringer's lactate 20 ml/kg body weight. Measurements and results. Before and after volume replacement, arterial pressure recordings, blood gas analysis, and an echocardiographic study were carried out. Left ventricular and aortic diameters were measured by the two-dimensional M-mode technique and velocity time integral of aortic flow by the pulsed color Doppler technique. From these data, stroke volume and cardiac output were calculated. Cardiac output (703 ± 204 vs 826 ± 166 ml/min, p < 0.005) and cardiac index (267 ± 69 vs 302 ± 55 ml/min per kg body weight, p < 0.01) changed significantly due to an appreciable elevation in stroke volume (5.2 ± 1.7 vs 5.8 ± 1.7 ml, p < 0.05), whereas heart rate was unaltered (140 ± 12 vs 142 ± 20 beats/min; NS). The change in blood pressure (32 ± 5 vs 38 ± 8 mm Hg, p < 0.01) was also significant. Cardiac index before and after volume replacement showed a significant inverse correlation with the severity of respiratory disease expressed as alveolar-arterial oxygen difference (A-aDO₂) (A-aDO₂ vs cardiac index before volume replacement: r = − 0.77, p < 0.001; after volume replacement: r = − 0.73, p < 0.005) or oxygenation index (oxygenation index vs cardiac index before volume replacement: r = − 0.73, p < 0.005; after volume replacement: r = − 0.73, p < 0.005). Changes in left ventricular diastolic diameter, left ventricular systolic diameter, and fractional shortening were not significant. Conclusions: These results indicate that the major regulator of left ventricular output in newborns with hypovolemic or cardiogenic shock is stroke volume and not heart rate and that cardiac output depends on the severity of the respiratory disease. Received: 21 March 1997 Accepted: 8 July 1997     

Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in pediatrics

OBJECTIVE: High-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) have been reported to improve oxygenation in children with acute hypoxemic respiratory failure (AHRF), but their roles in the treatment of AHRF remains unknown. The use of HFOV improves oxygenation by increasing lung recruitment. iNO can improve oxygenation in AHRF, but it may have limited efficacy in patients with poor lung inflation. Based on these findings, we hypothesized that the combined treatment of HFOV and inhalation of low-dose NO would improve oxygenation and survival in children with severe AHRF compared with children treated with conventional mechanical ventilation (CMV) or either treatment alone. SETTING: Tertiary pediatric intensive care units at seven academic centers. DESIGN: Post hoc analysis of data from children enrolled in a multicenter, randomized, masked study of the use of iNO in the treatment of AHRF. PATIENTS: A total of 108 pediatric patients with AHRF defined as an oxygenation index of >15 twice within 6 hrs. Mode of ventilation (HFOV or CMV) was determined by the patient's physician based on guidelines to maximize oxygenation. The patient was then randomized to treatment with or without iNO. Comparisons were made between patients who were treated with HFOV plus iNO (n = 14), HFOV alone (n = 12), CMV plus iNO (n = 35), and CMV alone (n = 38). INTERVENTIONS: Ventilation with CMV or HFOV with or without iNO. MEASUREMENTS AND MAIN RESULTS: We found that the change in Pao /Fio ratio was greatest in the HFOV plus iNO group compared with the other treatment groups at 4 hrs (p =.02) and 12 hrs (p =.01). After 24 hrs of treatment, both HFOV plus iNO and HFOV alone resulted in greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.005). After 72 hrs, treatment with HFOV alone resulted in a greater improvement in Pao2/Fio2 ratio than either CMV alone or CMV plus iNO (p =.03). There was no difference in predefined treatment failures between treatment groups. CONCLUSIONS: We conclude that the combination of HFOV with iNO causes a greater improvement in oxygenation than either treatment strategy alone in children with severe AHRF. We speculate that the enhanced lung recruitment by HFOV enhances the effects of low dose iNO on gas exchange.     

Alterations in circulating vasoactive substances in the critically ill —a comparison between survivors and non-survivors

Objective Regulation of circulatory homeostasis is based on several factors including various circulating vasoactive substances. Whether these regulators differ between survivors and non-survivors was investigated in critically ill patients.Design Prospective study.Setting Clinical investigation on a surgical intensive care unit of an university hospital.Patients 60 consecutive patients suffering from trauma (n=21) or postoperative complications (n=39) were studied prospectively. The patients were divided into survivors (n=27) and non-survivors (n=33). Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study.Measurements and results Endothelin-1, atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured from arterial blood samples using radioimmunoassay (RIA) or high-pressure liquid chromatography (HPLC) technique on the day of admission to ICU and during the following 5 days. Various hemodynamic parameters were also monitored during that period. The non-survivors showed elevated pulmonary artery pressure (PAP: 34.1±5.4 mmHg) and pulmonary capillary wedge pressure (PCWP: 20.3±7.3 mmHg) already at the beginning of the study. Cardiac index (CI) did not differ among the groups, whereas right ventricular ejection fraction (RVEF) decreased in the non-survivors. PaO₂/FIO₂ decreased only in the non-survivors, whereas VO₂ increased in the survivors (from 246±48 to 331±43 ml/min). Plasma levels of renin (from 206±40 to 595±81 pg/ml) and vasopressin (from 5.78±0.82 to 7.97±0.69 pg/ml) increased significantly in the non-survivors. Epinephrine and norepinephrine plasma concentrations were elevated in the non-survivors already at baseline and tremendously increased in these patients during the following days. ANP plasma levels significantly increased also only in the non-survivors (from 188±63 to 339±55 pg/ml) (p<0.05). Endothelin-1 decreased in the survivors, whereas it significantly increased in the non-survivors (from 3.62±0.68 to 9.37±0.94 pg/ml) during the study period (p<0.05). Analyses of co-variance revealed overall no significant correlation between circulating vasoactive substances and hemodynamics.Conclusions Systemic and regional regulators of the circulation were markedly changed by critical illness. In survivors, these regulators almost normalized within the study period of 5 days, whereas in non-survivors these alterations were even aggravated. It can only be speculated whether these regulator systems were influenced by activation of various mediator systems or whether they themselves influenced the negative outcome in the non-survivors.     

Predictors of respiratory function deterioration after transfer of critically ill patients

Objectives: Critically ill patients are often transferred due to the growing number of diagnostic procedures required to be performed outside the intensive care unit. These transfers have proved to be very critical. The aim of this study was to evaluate predictors for the deterioration of respiratory function in critically ill patients after transfer. Design: Prospective, clinical, observational study. Setting: 1800-bed university teaching hospital. Subjects: 98 mechanically ventilated patients were investigated during transfer. Measurement and main results: Before transfer, all patients were classified according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Therapeutic Intervention Scoring System (TISS). Haemodynamics and arterial blood gases were measured at 11 different times. Arterial oxgen tension (PaO₂), fractional inspired oxygen (FIO₂), PaO₂/FIO₂ ratio, lowest PaO₂/FIO₂ ratio, minimal PaO₂ and maximal FIO₂, APACHE II score, TISS before transfer, age and duration of transfer were analysed as potential predictors for deterioration of respiratory function after transfer. Variables were analysed using Classification and Regression Trees and Clustering by Response. In 54 transports (55 %) there was a decrease in the PaO₂/FIO₂ ratio, and a decrease of more than 20 % from baseline was noted in 23 of the transferred patients (24 %). Age > 43 years and FIO₂ > 0.5 were identified as predictors for respiratory deterioration. Conclusions: Our predictors were able to indicate deterioration after transfer correctly in 20 of 22 patients (91 %), combined with a false-positive rate in 17 of 49 (35 %). Received: 4 December 1997 Accepted: 14 August 1998