The outcome of cancer patients with acute respiratory distress syndrome

Objective

The objective of the study is to determine the 28-day mortality of critically ill cancer patients with acute respiratory distress syndrome (ARDS).

Design

This is a retrospective cohort study of patients enrolled in the ARDS Network randomized controlled trials.

Results

A total of 2515 patients did not have cancer, and 116 patients had cancer. Patients with cancer were older (median, 61 vs 49 years; P < .0001), more critically ill (the median Acute Physiology and Chronic Health Evaluation III score without cancer comorbidity was 105 for the cancer group compared with 87 for those without cancer; P < 0.0001), and more likely to have pneumonia or sepsis as cause of acute lung injury (79.31% vs 62.70%; P = .0011). The overall mortality at day 28 was 25.7%. Patients with cancer had significantly higher mortality (55.2%) compared with those without cancer (24.3%) (P < .0001). The odds ratio for mortality from ARDS at 28 days for cancer patients was 2.54 (95% confidence interval [CI], 1.570-4.120). Acute Physiology and Chronic Health Evaluation III score and age were found to be significant predictors of outcome in cancer patients with odds ratio of 1.034 (95% CI, 1.007-1.062; P = .0135) and 1.075 (95% CI, 1.024-1.129, P = .0036), respectively.

Conclusions

Cancer patients with ARDS have a significantly higher risk of death compared with those without cancer. The increased risk appeared to be mediated by increased severity of illness at presentation, as well as by age.     

糖皮质激素治疗对急性呼吸窘迫综合征患者预后的影响

目的：探讨早期应用糖皮质激素（GC）治疗对急性呼吸窘迫综合征（ARDS）患者预后的影响。方法回顾性分析成都军区总医院2008年1月至2011年12月收治的所有ARDS病例的临床资料,选择符合2012年柏林ARDS诊断标准的成人患者,根据是否采用过GC治疗将患者分为GC组与非GC组。GC组患者均在ARDS发生48 h内开始静脉使用低剂量GC（＜5 mg·kg-1·d-1,均换算为氢化可的松的剂量）治疗,激素种类为甲泼尼松龙、地塞米松,疗程为7～21 d;而非GC组为ARDS发生后未使用GC治疗。比较两组患者机械通气时间、重症加强治疗病房（ICU）住院时间、总住院时间、医疗费用和28 d生存率的差异。结果共纳入ARDS患者117例,其中GC组56例（占47.86%）,非GC组61例（占52.14%）。与非GC组比较,GC组机械通气时间明显缩短〔d：0（0,2.50）比2.00（0,2.50）,Z＝2.015,P＝0.044〕,28 d生存率明显升高〔71.43%（40/56）比50.82%（31/61）,χ2＝5.198,P＝0.023〕,ICU住院时间〔d：7.50（2.00,11.00）比4.00（1.00,9.00）,Z＝1.879, P＝0.060〕和总住院时间〔d：16.00（10.00,27.75）比15.00（7.00,28.00）,Z＝0.592,P＝0.552〕差异无统计学意义,但非GC组患者的医疗费用显著低于GC组〔万元：3.15（1.51,5.78）比4.39（1.66,10.88）,Z＝2.204,P＝0.028〕。结论早期使用GC治疗ADRS患者可改善预后,特别是28 d生存率。     

Recovery and long-term outcome in acute respiratory distress syndrome

Interest in longer-term outcomes after acute respiratory distress syndrome (ARDS) and the understanding of patterns of recovery have increased enormously over the past 10 years. This article highlights important advances in outcomes after ARDS and describes pulmonary outcomes, the most recent data on functional and neuropsychological disability in patients, health care cost, family caregivers, and early models of rehabilitation and intervention.     

急性呼吸窘迫综合征预后的影响因素分析

目的急性呼吸窘迫综合征（ARDS）预后的影响因素分析。方法纳入2009年1月至2012年2月在温州医学院附属第二医院重症医学科就诊的ARDS患者151例,其中死亡49例。对患者年龄、性别、血压、血糖、人体质量指数（BMI）、ARDS分级、急性病生理学和长期健康评价（APACHE）11评分、序贯器官衰竭估计（SOFA）评分、前降钙素原（PCT）、血管活性药物使用等相关因素进行单因素Logistic回归分析,选择有统计学意义的变量进行多因素Logistic回归分析。结果单因素Logistic分析发现,性别、血压、血糖对ARDS患者预后无统计学意义,而年龄、BMI、ARDS分级、APACHEII评分、SOFA评分、PCT、血管活性药物7个指标均影响ARDS患者的预后（P均〈0．05）。多因素logistic回归分析发现,影响ARDS患者预后的危险因素为ARDS分级（OR=6．895,95％CI=1．447～32．860）、年龄（OR=3．633,95％C1=1．333～9．906）APACHEU评分（OR=1．210,95％CI：1．033～1．417）及SOFA评分（O尺=1．676,95％CI=1．253～2．242）,而BMI是保护因素（OR=0．379,95％CI：0．168～0．856）。结论ARDS分级、APACHEII评分、SOFA评分及年龄是ARDS患者预后的不利因素,而BMI是保护因素。     

Prone positioning in patients with acute respiratory distress syndrome

Prone positioning is a technique used to treat patients with acute respiratory distress syndrome (ARDS). Nurses are ideally placed to initiate and manage prone positioning. This article examines the aetiology of ARDS and how nurses can identify this condition. Patient groups that benefit most from prone positioning are considered as well as the research evidence on the use of prone positioning in the treatment of ARDS. This article addresses nurse involvement in delivering therapy and suggests that nurses alert members of the multidisciplinary team to the possible use of this therapy.     

Antioxidant status in patients with acute respiratory distress syndrome

Objectives: Reactive oxygen species (ROS) have been implicated in the pathophysiology of ARDS. We investigated the pattern of antioxidants in plasma and ROS production by neutrophils in patients with ARDS over 6 days. Design: Observational study. Blood samples were taken when the diagnosis was made (D0) and after 3 (D3) and 6 days (D6) during therapy. Setting: Intensive care units at a University Hospital. Patients: Eight patients with ARDS were investigated, 17 healthy volunteers served as controls. Measurements and results: Plasma levels of ascorbate, α-tocopherol, retinol, β-carotene, selenium and lipid peroxidation products (MDA) were determined and the activities of the antioxidative enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in erythrocytes were measured. In addition, ROS production (superoxide anion and hydrogen peroxide) in activated neutrophils was assessed. Plasma levels of α-tocopherol, ascorbate, β-carotene and selenium were reduced from the onset of illness. MDA plasma levels were increased throughout the illness. ROS generation from neutrophils was normal on D0 and decreased to D6 in ARDS patients. Conclusion: The antioxidative system is severely compromised in patients with ARDS. Plasma levels of α-tocopherol, ascorbate, β-carotene and selenium are decreased. Elevated MDA levels provide further evidence of massive oxidative stress. The routine replacement of micronutrients according to recommended daily allowances was inadequate to compensate for the increased requirements. Received: 8 April 1998 Final revision received: 22 September 1998 Accepted: 5 October 1998     

Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients

Objective: To evaluate the prevalence and outcome of the acute respiratory distress syndrome (ARDS) among patients requiring mechanical ventilation. Design: A prospective, multi-institutional, initial cohort study including 28-day follow-up. Settings: Thirty-six French intensive care units (ICUs) from a working group of the French Intensive Care Society (SRLF). Patients: All the patients entering the ICUs during a 14-day period were screened prospectively. Hypoxemic patients, defined as having a PaO₂/FIO₂ ratio (P/F) of 300 mmHg or less and receiving mechanical ventilation, were classified into three groups, according to the Consensus Conference on ARDS: group 1 refers to ARDS (P/F: 200 mmHg or less and bilateral infiltrates on the chest X-ray); group 2 to acute lung injury (ALI) without having criteria for ARDS (200 < P/F ≤ 300 mmHg and bilateral infiltrates) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups. Results: Nine hundred seventy-six patients entered the ICUs during the study period, 43 % of them being mechanically ventilated and 213 (22 %) meeting the criteria for one of the three groups. Among all the ICU admissions, ARDS, ALI and group 3 patients amounted, respectively, to 6.9 % (67), 1.8 % (17) and 13.3 % (129) of the patients, and represented 31.5 %, 8.1 % and 60.2 % of the hypoxemic, ventilated patients. The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others (60 % vs 31 % p < 0.01). In group 3, 42 patients had P/F less than 200 mmHg associated with unilateral lung injury; mortality was significantly lower (40.5 %) than in the ARDS group. In the whole group of hypoxemic, ventilated patients, septic shock and severity indices but not oxygenation indices were significantly associated with mortality, while the association with immunosuppression revealed only a trend (p = 0.06). Conclusions: In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high. Received: 21 September 1998 Final revision received: 3 February 1999 Accepted: 3 May 1999     

The acute respiratory distress syndrome: Definitions,severity and clinical outcome An analysis of 101 clinical investigations

Objective To determine possible changes in outcome from acute respiratory distress syndrome (ARDS) and to compare severity of lung injury and methods of treatment from 1967 to 1994.Data sources Computerized (Medline, Current Contents) and manual (Cumulated Index Medicus) literature search using the key word and/or title ARDS.Study selection Only clinical studies published as full papers reporting data on both patient mortality (survival) and oxygenation index (PaO₂/FIO₂) were included. Single case reports, abstracts, reviews and editorials were excluded from evaluation.Data extraction Relevant data were extracted in duplicate, followed by quality checks on approximately 80% of data extracted.Data synthesis 101 papers reporting on 3264 patients were included: 48 studies (2207 patients) were performed in the USA, 43 studies (742 patients) in Europe and 10 studies (315 patients) elsewhere. Mortality reported in these studies was 53±22% (mean±SD), with no apparent trend towards a higher survival (1994: 22 studies, mortality 51±19%). The mean PaO₂/FIO₂ ratio remained unchanged throughout the observation period (118±47 mmHg). No correlation could be established between outcome and PaO₂/FIO₂ or lung injury score. Patients who underwent pressure-limited ventilation had a significantly lower mortality (35±20%) than patients on volume-cycled ventilation (54±22%) or patients for whom there was no precise information on ventilatory support (59±19%). Significantly lower PaO₂/FIO₂ ratios (61±17 mmHg) were observed in patients prior to extracorporeal lung assist, together with mortality rates in the range of those for conventionally treated patients (55±22%).Conclusions The mortality of ARDS patients remained constant throughout the period studied. Therefore, the standard for outcome in ARDS should be a mortality in the 50% range. Neither PaO₂/FIO₂ ratio nor lung injury score was a reliable predictor for outcome in ARDS. Patients might benefit from pressure-limited ventilatory support, as well as extracorporeal lung assist. Since crucial data were missing in most clinical studies, thus preventing direct comparison, we emphasize the importance of using standardized definitions and study entry criteria.     

乌司他丁在急性呼吸窘迫综合征的临床应用研究

目的观察乌司他丁对急性呼吸窘迫综合征(ARDS)的临床作用。方法选择56例ICU收治的ARDS患者作为研究对象,采用随机双盲的方法分为乌司他丁治疗组(A组)和糖皮质激素治疗组(B组)两组,分别静脉推注乌司他丁60万U/d和甲基强的松龙120 mg/h,观察用药后1 h患者收缩压、尿量、心率、氧合指数的改变以及1周后胃液pH值和潜血试验、血糖的变化,比较两组患者真菌感染发生率、带管时间、平均住院时间和死亡率的变化。结果与治疗前相比,用药后1 hA、B两组收缩压升高(18.6±4.3)mm Hg和(16.7±5.1)mm Hg,尿量增加(35.5±9.5)mL和(37.5±8.7)mL,心率下降(21.4±7.3)次/m in和(19.8±6.9)次/m in,氧合指数增加(23.6±11.2)mm Hg和(20.9±10.6)mm Hg;1周后A、B两组胃液pH值分别下降0.03±0.01和0.08±0.02,潜血试验阳性率分别为14.86%和32.14%,血糖升高(1.42±0.09)μmol/L和(5.73±0.13)μmol/L,真菌感染发生率分别为21.43%和67.86%,带管时间、平均住院时间和死亡率分别为36.5 d和53.4d、52.7 d和72.6 d、28.57%和42.86%。结论乌司他丁具有抗休克、改善循环、改善氧合、降低平均住院时间和死亡率的作用,而静注乌司他丁后应激性溃疡、高血糖和真菌感染发生率均较低,可望代替糖皮质激素应用于ARDS的临床救治。     

Protective ventilation of patients with acute respiratory distress syndrome

In a recent issue of the British Journal of Anaesthesia, Moloney and Griffiths reviewed clinically pertinent issues surrounding the management of the acute respiratory distress syndrome (ARDS) patient, particularly as it pertains to the treatment of ventilator induced/associated lung injury (VILI). In addition to highlighting the important observations that have contributed to further our understanding of the relationship between the mechanical ventilator and inflammatory lung injury, the authors also offer a concise reappraisal of the clinical strategies used to minimize VILI in ARDS. Special emphasis is placed on the theory of biotrauma, which attempts to explain how multi-organ failure may develop in patients who ultimately succumb to this syndrome.     

Protective ventilation of patients with acute respiratory distress syndrome

In a recent issue of the British Journal of Anaesthesia, Moloney and Griffiths reviewed clinically pertinent issues surrounding the management of the acute respiratory distress syndrome (ARDS) patient, particularly as it pertains to the treatment of ventilator induced/associated lung injury (VILI). In addition to highlighting the important observations that have contributed to further our understanding of the relationship between the mechanical ventilator and inflammatory lung injury, the authors also offer a concise reappraisal of the clinical strategies used to minimize VILI in ARDS. Special emphasis is placed on the theory of biotrauma, which attempts to explain how multi-organ failure may develop in patients who ultimately succumb to this syndrome.     

Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome

Purpose

Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients.

Methods

We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling.

Results

Of 399 ARDS patients, 271 (68 %) were CMV seropositive and reactivation occurred in 74 (27 %) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95 % CI 1.51–4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95 % CI 0.86–2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95 % CI 0.58–1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23 % (95 % CI 6–41) by day 30 (risk difference 4.4, 95 % CI 1.1–7.9).

Conclusion

CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.

     

Incidence of acute respiratory distress syndrome and its relation to age

PURPOSE: The incidence of acute respiratory distress syndrome (ARDS) was previously considered to be relatively low, at less than 10 cases per 100,000 inhabitants per year, but recent reports suggest a higher incidence, especially in elderly patients. The objective was to determine the incidence and mortality of ARDS in our setting, both overall and by age group. MATERIALS AND METHODS: We conducted a prospective, observational study of patients older than 14 years, admitted to the intensive care units of all hospitals in a province of southern Spain (Granada) during a 5-month period in 2001. American-European Consensus Conference criteria for ARDS were used. Patients were divided into 5 age groups, and the hospital mortality was recorded. RESULTS: During the study period, 61 Granada-residing patients developed ARDS criteria. This represents an overall incidence of 23 cases per 100,000 inhabitants per year in the province. The incidence of ARDS in the age groups of 15 to 29, 30 to 44, 45 to 59, 60 to 74, and older than 74 years was 4.6, 13.6, 21.6, 51, and 73.9 cases per 100,000 inhabitants per year, respectively. The overall hospital mortality rate was 66%. CONCLUSIONS: The incidence of ARDS is higher than reported a decade ago and is especially elevated in the elderly. The mortality remains high.     

Translaryngeal tracheostomy in acute respiratory distress syndrome patients

OBJECTIVE: To prevent gas exchange deterioration during translaryngeal tracheostomy (TLT) in patients with acute respiratory distress syndrome (ARDS) ventilation is maintained through a small diameter endotracheal tube (ETT; 4.0 mm i.d.) advanced beyond the tracheostoma. We report on the feasibility of uninterrupted ventilation delivered through a high-resistance ETT in ARDS patients, and relevant ventilatory adjustments and monitoring. DESIGN AND SETTING: Prospective, observational clinical study in an eight-bed intensive care unit of a university hospital. Patients: Eight consecutive ARDS patients scheduled for tracheostomy. INTERVENTIONS: During TLT volume control ventilation was maintained through the 4.0-mm i.d. ETT. Tidal volume, respiratory rate, and inspiratory to expiratory ratio were kept constant. Fractional inspiratory oxygen was 1. Positive end expiratory pressure (PEEP) set on the ventilator (PEEP(vent)) was reduced to maintain total PEEP (PEEP(tot)) at baseline level according to the measured intrinsic PEEP (auto-PEEP). MEASUREMENTS AND MAIN RESULTS: Data were collected before tracheostomy and while on mechanical ventilation with the 4.0-mm i.d. ETT. Neither PaCO(2) nor PaO(2) changed significantly (54.5+/-10.0 vs. 56.4+/-7.0 and 137+/-69 vs. 140+/-59 mmHg, respectively). Auto-PEEP increased from 0.6+/-1.1 to 9.8+/-6.5 cmH(2)O during ventilation with the 4.0-mm i.d. ETT. By decreasing PEEP(vent) we obtained a stable PEEP(tot) (11.4+/-4.3 vs. 11.8+/-4.3 cmH(2)O), and end-inspiratory occlusion pressure (26.7+/-7.4 vs. 28.0+/-6.6 cmH(2)O). Peak inspiratory pressure rose from 33.8+/-8.1 to 77.8+/-12.7 cmH(2)O. CONCLUSIONS: The high-resistance ETT allows ventilatory assistance during the whole TLT procedure. Assessment of stability in plateau pressure and PEEP(tot) by end-inspiratory and end-expiratory occlusions prevent hyperinflation and possibly barotrauma.     

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome

Purpose

To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).

Patients and methods

We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.

Main outcomes

We included 1899 patients with ARDS in this study. The relationship between maximum PaCO₂ in the first 48 h and mortality suggests higher mortality at or above PaCO₂ of ≥50 mmHg. Patients with severe hypercapnia (PaCO₂ ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO₂/FiO₂ ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; p = 0.032).

Conclusions

Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.

Trial registration

Clinicaltrials.gov identifier, NCT01093482.

     

Effect of acute lung injury and acute respiratory distress syndrome on outcome in critically ill trauma patients

OBJECTIVE: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known to be associated with increased mortality and costs in trauma patients. We estimated the independent impact of these conditions on mortality and cost, beyond the severity of injury with which they are correlated. DESIGN: One-year prospective cohort. PATIENTS AND SETTING: All trauma patients admitted to the intensive care unit in a level I center were evaluated daily for ALI/ARDS using the American-European Consensus Conference definition. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were hospital mortality and costs. Logistic regression was used to model hospital mortality in relation to the presence of ALI and ARDS, adjusting for trauma severity (Injury Severity Score), Acute Physiology Score, and age. Hospital costs were modeled using multivariable linear regression. Of the 1,296 trauma patients surviving beyond the first day, 4% experienced ALI (defined as Pao2/Fio2 of 201-300 mm Hg) and 12% had ARDS (Pao2/Fio2 < or = 200 mm Hg). The crude relative risk of mortality was 2.24 (95% confidence interval, 0.92-5.45) in patients with ALI and 3.84 (95% confidence interval, 2.41-6.13) in patients with ARDS compared with those without ALI/ARDS. However, there was no association of mortality with ALI (relative risk, 0.99; 95% confidence interval, 0.29-3.36) or with ARDS (relative risk, 1.23; 95% confidence interval, 0.63-2.43) after adjustment for age, Injury Severity Score, and Acute Physiology Score. Among patients of comparable age, severity score, and length of stay, median cost was 20% to 30% higher for those with ALI/ARDS. CONCLUSIONS: There is no additional mortality associated with ALI/ARDS above and beyond the factors that can be measured at intensive care unit admission. Therefore, mortality in trauma patients is explained by injury severity at admission and is not affected by the subsequent occurrence of ALI/ARDS. Nonetheless, ALI/ARDS was associated with increased intensive care unit stay and hospital cost, independent of trauma severity.     

Incidence and prognostic value of right ventricular failure in acute respiratory distress syndrome

Objective  To analyse the incidence and the impact on outcome of right ventricular failure (RVF) in patients with acute respiratory distress syndrome (ARDS). Patients and methods  A total of 145 ARDS patients included in the previously published French Pulmonary Artery Catheter (PAC) study were randomly assigned to receive a PAC. All patients were ventilated according to a strategy aimed at limiting plateau pressure. The RVF was defined by the concomitant presence of: (1) a mean pulmonary artery pressure (MPAP) > 25 mmHg, (2) a central venous pressure (CVP) higher than pulmonary artery occlusion pressure (PAOP) and (3) a stroke volume index < 30 mL m⁻². Results  Right ventricular failure was present in 9.6% of patients. Mortality was 68% at day-90 with no difference between patients with RVF (RVF+) and without RVF (71 vs. 67%, respectively). SAPS II, PaO₂/FiO₂ and PaCO₂ were similar in both groups. Tidal volume and I/E ratio were significantly higher in RVF+ (9.7 ± 2.8 vs. 8.6 ± 1.8 ml m⁻² and 0.7 ± 0.5 vs. 0.5 ± 0.2). Plateau pressure tended to be higher in RVF+ (28 ± 6 vs. 25 ± 6 cmH₂O, NS). In multivariate analysis, PaO₂/FiO₂, mean arterial pressure, arterial pH, SvO₂, MPAP and presence of CVP > PAOP, but not RVF, were independently associated with day-90 mortality. Conclusion  In this group of patients investigated early in the course of ARDS and ventilated according to a strategy aimed at limiting plateau pressure, the presence of RVF was about 10%. Unlike MPAP and the presence of CVP > PAOP, RVF at this early stage did not appear as an independent factor of mortality. This article is discussed in the editorial available at: doi:.