Management of Refractory Hypoxemic Respiratory Failure secondary to Diffuse Alveolar Hemorrhage with Venovenous Extracorporeal Membrane Oxygenation

Evanpaul Gill²

Mohamed A. Fayed^1,2,

Elliot Ho^1,2

University of California San Francisco - Fresno Medical Education Program

¹Pulmonary and Critical Care Division

²Department of Internal Medicine

Fresno, CA USA

Abstract

Uncontrolled bleeding has been a relative contraindication for the use of venovenous extracorporeal membrane oxygenation (VV ECMO), but current practice is relatively institution dependent. With the recent advances in circuit technology and anticoagulation practices, the ability to manage patients with ongoing bleeding with ECMO support has increased. We report the case of a 66-year-old patient with refractory hypoxemic respiratory failure secondary to diffuse alveolar hemorrhage (DAH) from underlying anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis who was successfully supported through his acute illness with VV ECMO. ECMO is often used to manage patients with refractory hypoxemic respiratory failure but the usage in the setting of DAH is less known given the risk of bleeding while receiving anticoagulation. Our patient was successfully managed without anticoagulation during his initial ECMO course and his respiratory failure rapidly improved after cannulation. Once managed through the acute phase of his illness and treatment started for his underlying disease process, anticoagulation was started. After being de-cannulated from ECMO and a 3 week stay in the acute rehabilitation unit, our patient was discharged home with complete recovery from his illness. We highlight that patients with refractory hypoxemic respiratory failure and suspicion of DAH as an etiology, ECMO without anticoagulation should be considered as supportive salvage therapy until the underlying process can be treated.

Case Presentation

A 66-year-old man presented with cough, fever, and dyspnea for 1 week. Upon presentation he was found to be in hypoxemic respiratory failure with bilateral pulmonary infiltrates on chest x ray (Figure 1) and positive testing for Influenza A.

Figure 1. Portable AP of chest on initial presentation showing bilateral infiltrates more prominent on the right.

He had an elevated creatinine of 8.1 mg/dl and an acute anemia with a hemoglobin of 7.4 g/dl during the initial work up. He was intubated on hospital day one and transferred to our center for a higher level of care early morning on hospital day two. He developed refractory hypoxemic respiratory failure despite maximum ventilator support as well as standard acute respiratory distress syndrome (ARDS) treatment including neuromuscular blockade. Prone positioning was not possible secondary to hemodynamic instability during the initial treatment plan. Infectious and autoimmune work up was sent. A thoracic CT scan showed extensive bilateral consolidation (Figure 2).

Figure 2. A representative image from the thoracic CT scan showing extensive bilateral consolidation.

At this point a decision was made to apply venovenous double lumen (VVDL) ECMO support as a supportive salvage therapy pending further evaluation into the etiology of his respiratory failure and ARDS. Etiologies at this point included severe influenza infection and DAH from an underlying vasculitis. Anticoagulation with heparin was not initiated given the significant anemia requiring multiple blood transfusions at that point. BUN was elevated, but no other signs of acute gastrointestinal bleeding were identified. Given the underlying renal failure, continuous renal replacement therapy (CRRT) was started on hospital day 2 with citrate used as the anticoagulant. After initiation of ECMO, he improved significantly in the next 72 hours, however, he developed bleeding from the endotracheal tube on day 4. Bronchoscopy was subsequently performed and showed bloody secretions throughout the respiratory bronchial tree, consistent with DAH. His ECMO course had been unremarkable with no thrombotic complications requiring changing of the circuit. Target flows were achieved with a Cardiohelp centrifugal pump and his Avalon 31F double lumen catheter was without complication. On day 5, his autoimmune panel showed a positive ANCA, with myeloperoxidase elevated at 82 AU/ml and serine protease elevated at 314 AU/ml. His anti-nuclear antibody (ANA) was also positive with his titer at 1:2,560. After rheumatology consultation, he was diagnosed with ANCA associated vasculitis with pulmonary hemorrhage and renal failure. His influenza infection was thought to be the trigger for the exacerbation of his underlying autoimmune disease. He was initiated on pulse dose steroids and plasmapheresis with significant clinical improvement and was de-cannulated from ECMO on day 8 with extubation following shortly afterward. He later had renal biopsy performed and it showed diffuse crescentic glomerulonephritis secondary to ANCA vasculitis. He was able to discontinue dialysis after requiring 8 days of CRRT and a further 3 weeks of intermittent hemodialysis. A chest x-ray showed complete clearing of the consolidation (Figure 3).

Figure 3. Chest x-ray just prior to discharge showing complete clearing of the consolidations.

He was eventually discharged home after a 3-week period in acute inpatient rehab.  

Discussion

VV ECMO is increasingly being used as a viable treatment option in patients with refractory acute respiratory failure, especially in patients with underlying ARDS. The ability to allow lung protective ventilation by use of an extracorporeal circuit is of significant value in the acute phase of severe respiratory failure. The general principle of VV ECMO involves removing deoxygenated blood from a venous catheter and passing it through a closed circuit which is comprised of a centrifugal pump and membrane oxygenator (1). This membrane oxygenator takes over the function of the diseased lungs and allows gas exchange to occur, mainly oxygenating the blood and removing carbon dioxide.¹ This blood is then returned into the venous circulation and eventually makes it to the systemic circulation to oxygenate the tissues.

Given that native blood is being passed through an artificial circuit, the risk for thromboembolism is thought to be relatively high. The pathophysiology behind this risk stems from contact of blood components with the artificial surface of the ECMO circuit (2). Proteins found in blood, mainly albumin and fibrinogen, will stick to the artificial surface (2). This results in other blood components congregating, which leads to the formation of a protein layer that servers as an anchor for platelet activation and the formation of insoluble fibrin clots (2). Given the risk of thromboembolism, Extracorporeal Life Support (ELSO) guidelines recommend routine anticoagulation for patients undergoing extracorporeal support (3).

The major complications regarding anticoagulation in the setting of ECMO is bleeding (4). The risk generally comes from acquired thrombocytopenia and anticoagulation (2). ELSO has guidelines regarding management of anticoagulation in VV ECMO but the current practice is relatively institution dependent. This was highlighted in a systematic review done by Sklar and colleagues (4) that investigated many different approaches to anticoagulation for patients on VV ECMO. The main anticoagulant used in those studies was unfractionated heparin and the means to measure its effect was activated clotting time (ACT) and partial thromboplastin time (PTT). They concluded that currently there is no high-quality data that can be employed in decision making regarding anticoagulation for patient’s on VV ECMO support for respiratory failure and that randomized controlled trials are needed for high quality evidence (4). Our own institution’s protocol uses unfractionated Heparin for anticoagulation with a PTT goal of 60-80.

The traditional risk of anticoagulation with ECMO has improved as the component technology of the ECMO circuit has progressed (2). Development of heparin coated inner tubing along with shorter circuit lengths are recent strategies that have been employed to help decrease the amount of thrombotic complications (2). ECLS guidelines state that patients can be managed without anticoagulation if bleeding cannot be controlled with other measures and that the use of high flow rates is recommended to help prevent thrombotic complications (3). The strategies mentioned above are non-chemical ways of preventing thrombosis and could potentially allow management of VV ECMO patients without anticoagulation for the initial period. This was demonstrated in a case report done by Muellenbach and colleagues (5). In their case series, they describe three cases of trauma patients with intracranial bleeding and severe ARDS refractory to conventional mechanical ventilation that were managed with VV ECMO without systemic anticoagulation for a prolonged time period. In their situation, anticoagulation could not be given secondary to severe traumatic brain injury (TBI) and intracranial bleeding (5). They stated that because newer circuits are completely coated by heparin and because circuit lengths have been shortened by specialized diagonal pumps and oxygenators, systemic anticoagulation can be reduced (5)

VV ECLS, as mentioned above, is commonly used in acute respiratory failure but use of VVECLS in DAH is a less known use due to the risk of anticoagulation in this clinical setting. Per ECLS guidelines, one of the relative contraindications for initiation of ECLS is risk of systemic bleeding from anticoagulation (3), and patients with DAH definitely fit this risk profile. But as mentioned above; with improving shortened ECMO circuits, use of heparin coated tubing, and high flow rates, the ability to initially manage patients without systemic anticoagulation until they are stabilized is very important in clinical settings such as our patient with DAH. Many case reports have been published that highlight the successful management of acute respiratory failure due to DAH with VV ECMO (6,7). Our patient was initially managed without systemic anticoagulation and required multiple blood transfusions given the significant bleeding appreciated from the endotracheal tube. Once the diagnosis of ANCA related DAH was made and the appropriate treatment initiated, bleeding significantly decreased and the patient was able to be started on anticoagulation. This highlights that patients with suspicion of DAH as an etiology of respiratory failure not be excluded from consideration VV ECMO as supportive salvage therapy given the potential for great clinical outcome if managed through the acute phase of bleeding.

References

1. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011 Nov 17;365(20):1905-14. [CrossRef] [PubMed]
2. Mulder M, Fawzy I, Lance MD. ECMO and anticoagulation: a comprehensive review. Neth J Crit Care. 2018;26:6-13.
3. Brogan TV, Lequier L, Lorusso R, MacLaren G, Peek G. Extracorporeal Life Support: The ELSO Red Book. Fifth Edition. Extracorporeal Life Support Organization; 2017. Thomas V. Brogan and Laurance Lequier (eds).
4. Sklar MC, Sy E, Lequier L, Fan E, Kanji HD. Anticoagulation practices during venovenous extracorporeal membrane oxygenation for respiratory failure. A systematic review. Ann Am Thorac Soc. 2016 Dec;13(12):2242-50. [CrossRef] [PubMed]
5. Muellenbach RM, Kredel M, Kunze E, Kranke P, Kuestermann J, Brack A, Gorski A, Wunder C, Roewer N, Wurmb T. Prolonged heparin-free extracorporeal membrane oxygenation in multiple injured acute respiratory distress syndrome patients with traumatic brain injury. J Trauma Acute Care Surg. 2012 May;72(5):1444-7. [CrossRef] [PubMed]
6. Abrams D, Agerstrand CL, Biscotti M, Burkart KM, Bacchetta M, Brodie D. Extracorporeal membrane oxygenation in the management of diffuse alveolar hemorrhage. ASAIO J. 2015 Mar-Apr;61(2):216-8. [CrossRef] [PubMed]
7. Patel JJ, Lipchik RJ. Systemic lupus-induced diffuse alveolar hemorrhage treated with extracorporeal membrane oxygenation: a case report and review of the literature. J Intensive Care Med. 2014 Mar-Apr;29(2):104-9. [CrossRef] [PubMed]

Cite as: Gill E, Fayed MA, Ho E. Management of refractory hypoxemic respiratory failure secondary to diffuse alveolar hemorrhage with venovenous extracorporeal membrane oxygenation. Southwest J Pulm Crit Care. 2019;18(5):135-40. doi: https://doi.org/10.13175/swjpcc007-19 PDF

Ultrasound for Critical Care Physicians: Two’s a Crowd

A 43 year old previously healthy woman was transferred to our hospital with refractory hypoxemia secondary to acute respiratory distress syndrome (ARDS) due to H1N1 influenza. She had presented to the outside hospital one week prior with cough and fevers. Chest radiography and computerized tomography of the chest revealed bilateral airspace opacities due to dependent consolidation and bilateral ground glass opacities. A transthoracic echocardiogram at the time of the patient’s admission was reported as not revealing any significant abnormalities.

At the outside hospital she was placed on mechanical ventilation with low tidal volume, high Positive end-expiratory pressure (20 cm H20), and a Fraction of inspired Oxygen (FiO2) of 1.0. Paralysis was later employed without significant improvement.

Upon arrival to our hospital, patient was severely hypoxemic with partial pressure of oxygen / FiO2  (P/F) ratio of 43. She was paralyzed with cis-atracurium and placed on airway pressure release ventilation (APRV) with the following settings (pressure high 28 cm H2O, pressure low 0 cm H2O, time high 5.5 sec, time low 0.5 sec). The patient remained severely hypoxemic with on oxygen saturation in the high 70 percent range.

A bedside echocardiogram was performed (Figures 1 and 2).

Figure 1. Subcostal long axis echocardiogram.

Figure 2. Subcostal short axis echocardiogram

What abnormality is demonstrated by the short and long axis subcostal views? (Click on the correct answer for an explanation)

1. Acute cor pulmonale likely due to ARDS
2. Acute myocardial infarction
3. Low left-sided ejection fraction
4. Pericardial tamponade

Cite as: Abukhalaf J, Boivin M. Ultrasound for critical care physicians: two's a crowd. Southwest J Pulm Crit Care. 2016 Mar;12(3):104-7. doi: http://dx.doi.org/10.13175/swjpcc028-16 PDF

January 2016 Critical Care Case of the Month

Sandra L. Till, DO

Banner University Medical Center Phoenix

Phoenix, AZ USA  

History of Present Illness

The patient is an 18-year-old woman who was driving to high school on a frontage road when she fell asleep at the wheel and her car rolled over. She was wearing her seatbelt but there was no airbag deployment. She did not lose consciousness and she was responsive and answering questions at the scene. She self-extricated from the vehicle. She had left arm pain with a boney deformity and she walked to the ambulance that transferred her to the hospital emergency department (ED).

Upon arrival in the ED she appeared pale and had difficulty breathing. In addition to her arm pain with an obvious left humeral fracture she also complained of upper abdominal and anterior chest pain. O2 saturation was initially 90% but declined to 70%.

Which of the following should be ordered immediately? (Click on the correct answer to proceed to the second of six panels)

1. Begin intravenous lines with large bore needles
2. X-ray of humerus
3. Hemoglobin and hematocrit
4. 1 and 3
5. All of the above

Cite as: Till SL. January 2016 critical care case of the month. Southwest J Pulm Crit Care. 2016;12:6-12. doi: http://dx.doi.org/10.13175/swjpcc151-15 PDF 

December 2015 Critical Care Case of the Month

Samir Sultan, DO 

Banner University Medical Center Phoenix

Phoenix, AZ 

History of Present Illness

The patient is a 32-year-old woman who presented with flank pain for 3 days to an outside hospital. She was diagnosed with pyelonephritis and begun on ceftriaxone. She was discharged against medical advice on cephalexin.

She returned to the same hospital 3 days later by ambulance with labored breathing and weakness and was emergently intubated. She was transferred for ventilator management and respiratory failure.

Past Medical History

She has a long history of poorly controlled diabetes mellitus.

Physical Examination

She is orally intubated and sedated.

Vitals: Temperature - 100.9º F, Blood Pressure - 117/75 mm Hg, Heart Rate - 148 beats per minute,  Respiratory Rate - 31 breaths/min, SpO2 - 88 % on assist control of 30, tidal volume of 350 mL, PEEP 15, and an FiO2 100%.

There is scatted rhonchi and rales but the remainder of the physical examination is unremarkable.

Radiography

Her admission portable chest X-ray is shown in Figure 1.

Figure 1. Admission portable AP of the chest.

Which of the following should be ordered as part of her initial work-up? (Click on the correct answer to proceed to the second of five panels).

1. Administer broad spectrum antibiotics
2. Blood and urine cultures
3. Rapid influenza test
4. 1 and 3
5. All of the above

Cite as: Sultan S. December critical care case of the month. Southwest J Pulm Crit Care. 2015;11(6):246-51. doi: http://dx.doi.org/10.13175/swjpcc147-15 PDF

Fluid in the Management of the Acute Respiratory Distress Syndrome

Sanjaya Karki* (drsanjaya.karki@yahoo.com)

Yong-Jie Yin* (corresponding author)-yongjieyin2003@yahoo.com.cn

Jing-Xiao Zhang*

Nijamudin Samani*

Dipesh Pradhan^‡

Sangeeta Singh Deuja (Karki)^†

Reshma Karki^#

Raghvendra Thakur**

Nan Zhao***

*Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, China

^‡ First hospital of Jilin University, China

^†University of Huddersfield, UK

^#Sri Birendra Hospital, Nepal

**Second Hospital of Jilin University

***Department of Chemistry, Jilin University, Changchun, China

Abstract

Introduction

Non-cardiogenic pulmonary edema is the hallmark of the acute respiratory distress syndrome (ARDS). The amount of fluid and which fluid should be used in these patients is controversial. 

Methods

43 patients with ARDS treated in the intensive care unit (ICU) of the Second Hospital, Jilin University between November 1, 2011-November 1, 2012 were prospectively analyzed and was observational. Volume and the type of fluid administered were compared to 90 day mortality and the 24 and 72 hour sequential organ failure assessment (SOFA) score, lactate level, oxygenation index (PaO2/FiO2), duration of ICU stay, total ventilator days, and need for continuous renal replacement therapy (CRRT).

Results

Mortality was increased when hydroxylethyl starch (HES) was used in the first day or plasma substitutes were used during the first 3 days (P<0.05, both comparisons). Volumes of fluid >3000 ml during the first 24 hours or >8000 ml during the first 72 hours were associated with higher SOFA scores at 24 and 72 hours (P<0.05, both comparisons). Colloid, especially higher volume colloid use was also associated with increased SOFA scores at either 24 or 72 hours.

Conclusions

Limiting the use of colloids and the total amount of fluid administered to patients with ARDS is associated with improved mortality and SOFA scores.

Introduction

Acute lung disease secondary to non-cardiogenic pulmonary edema has been termed the adult respiratory distress syndrome (ARDS) since first described in 1967 by Ashbaugh et al. (1,2). ARDS was later defined at a consensus conference in Berlin (3). The Berlin definition is based on timing, chest imaging, origin of edema and oxygenation.

Despite the presence of fluid within the alveoli, it has been unclear whether a conservative strategy or liberal strategy improves outcomes. The ARDS Clinical Trials Network demonstrated that a conservative strategy based on pulmonary artery wedge pressures or central venous pressures improved lung function and shortened the duration of mechanical ventilation although there was no mortality benefit (4). However, whether fluid replacement with colloid or crystalloid in ARDS results in better outcomes remains unknown.

Recently, there have been reports of increased mortality with the use of hydroxylethyl starch (HES) in sepsis (5).  Because sepsis is the most common cause of ARDS (1) this caused us to examine the use of colloids in ARDS. We found that use of colloids was associated with clinically worsening and increases mortality compared to low volumes of crystalloid in ARDS.

Materials and Methods

Subjects

This was an observational study of ARDS patients admitted to the intensive care unit (ICU) of the Norman Bethune College of Medicine, Jilin University Second Hospital, Changchun, China was conducted from November 1, 2011 to November 1, 2012.

ARDS was defined using the Berlin criteria (3).

Study Procedures

Patients were randomly divided into two groups. In one group patients were administered both crystalloid and colloid for the first 3 days of their ICU admission with ARDS. In the other group only crystalloid was used. The use of which colloid and the volume administered was left to the clinical discretion of the attending physician based on the clinical needs of the patient. Other treatment modalities such as the mode of ventilation and nutritional support were also left to the discretion of the patient although the tidal volume was kept < 7ml/kg.

Data was collected for the first 3 days of admission to the ICU. Clinical data recorded included sequential organ failure assessment (SOFA) scores, the use and amount of colloid or crystalloid, duration of ICU stay, ventilator days, need for continuous renal replacement therapy (CRRT), lactate and PaO2/FIO2. When patients received both colloid and crystalloid, volume was calculated as the sum of the volume of each. Mortality was the 90 day mortality rate.

Statistics

The data was recorded and compared using SPSS software and reported as mean + standard deviation. Comparisons between groups were performed by Student’s t-test. P values of less than 0.05 were considered significant.

Results

Patients. There were 43 patients (20 F, 23 M). The mean age was 62.7 + 18.9 years (range 20 to 85 years). The causes of ARDS was serious lung infection in 16 patients,  sepsis in 9 patients, trauma in 2 patients, and pancreatitis in 2 patients. The cause was unknown in 14 patients.

Volume of fluid. The results with differing volumes of fluid administered in the first 24 hours are shown in Table 1. [Editor's note: It may be necessary to enlarge the view on your browser in order to adequately display the tables.]

Table 1. Results based on volume of fluid used in the first day.

Mortality was unaffected by the volume of fluid used in the first 24 hours. However, the SOFA score at 24 and 72 hours was increased with volumes >3000 ml administered during the first 24 hours (P<0.05, both comparisons). The lactate level and the frequency of CRRT approached significance when volumes of >3000 ml were administered during the first 24 hours (P=0.05, both comparisons).

The results with volumes of greater or less than 8 liters are shown in table 2.

Table 2. Results based on volume of fluid used in the first 72 hours.

 

There were no significant effects of administration of greater or less than 8000 ml over 72 hours.

Type of fluid. Patients who received both crystalloid and colloid received 30 + 5% of the total volume as colloid during the first day of ICU admission. The results of administration of crystalloid compared to crystalloid and colloid during the first 24 hours are shown in Figure 3.

Table 3. Results based on type of fluid used in the first day of ICU admission.

There was no difference in mortality. The use of crystalloid alone was associated with a lower SOFA score at 72 hours (P<0.05). CRRT was more often needed for those patients given both crystalloid and colloid during the first 24 hours (P=0.05).

The results when albumin was used during the first 24 hours are in Table 4.

Table 4. Results based on albumin usage during the first day.

There was no significant effect on any of the measured outcomes when albumin was used in the first 24 hours.

The results with the use of plasma during the first 24 hours are shown in Table. 5.

Table 5. Results based on plasma usage during first day.

An increase in mortality approached statistical significance if plasma was used during the first 24 hours (P=0.05). The SOFA score was significantly higher at 72 hours if plasma used during the first day (P=0.01). The remaining outcomes were unchanged.

Results with hydroxylethyl starch (HES) use are shown in Table 6.

Table 6. Results based on hydroxylethyl starch (HES) usage during the first day.

  

Mortality was significantly higher if HES was used during the first 24 hours (P<0.05). In addition the SOFA scores were significantly higher at 24 and 72 hours if HES was administered during the first 24 hours (P<0.05, both comparisons). The lactate level was also significantly higher at 24 hours and 72 hours (P<0.05, both comparisons). The need for CRRT and the PaO2/FiO2 ratio approached significance (P=0.05, both comparisons).

Volume of colloid. The use of colloids affected several outcomes. Therefore, the amount of colloid used was examined (Table 7).

Table 7. Results based on volume of colloid used during first day. 

If colloid was used, mortality approached significance based on the volume of colloid used during the first 24 hours (P=0.05). Higher volumes of administered colloid (≥1000ml) were associated with a higher SOFA score at 72 hours (P=0.01). Lactate levels were significantly higher at 24 and 72 hours if colloid was used (P=0.04, both comparisons).PaO2/FiO2 was lower higher volumes of colloid usage (P=0.04).

Plasma, albumin or plasma substitutes during the first 72 hours. Some outcomes were higher with the use of colloids during the first 24 hours. Therefore, usage of plasma or albumin during the first 3 days was examined (Table 8).

Table 8. Effect of using of plasma or albumin during the first 3 days.

There was no significant effect on any of the outcomes with the use of plasma or albumin during the first 72 hours.

The effects of plasma substitutes during the first 72 hours are shown in Table 9.

Table 9. Results of using plasma substitutes during the first 3 days.

Higher mortality was associated with the use of plasma substitutes during the first 3 days (P=0.02).  SOFA scores at 24 and 72 hours were also increased with plasma substitute usage (P=0.03 and P=0.002 respectively). Higher Lactate levels were also observed at 24 hours and 72 hours (P<0.01, both comparisons).

Discussion

In the hospital setting there are two types of fluid physicians administer to patients-colloid or crystalloid. Crystalloid is easily accessible and can be stored at room temperature. The main purpose of this study was to compare the two different fluids and the volume fluid used. We found that use of certain colloids, particularly higher volumes, was associated with increased mortality and poorer SOFA scores.

There was increased mortality with HES and plasma substitutes and plasma approached statistical significance. This is consistent with studies done in sepsis where HES has been associated with increased mortality (5).  In contrast, there was no increase in mortality with albumin or adverse clinical outcomes, suggesting it was safe to use. The mechanism accounting for the adverse effects of colloids in ARDS and sepsis is unknown. However, the pharmokinetics of HES is known to be different from albumin and may play a role in the mortality rates (6). 

We found that administration of smaller volumes of fluid was associated with improved outcomes. This confirms previous studies done in ARDS demonstrating that a conservative strategy improves outcomes. Like the ARDS Network larger, multi-center study out smaller study was unable to find a reduction in mortality with lower volumes of fluid used.  From our studies it is unclear whether volume or the type of fluid is most important in determining survival. The data would seem to suggest that both are important. We also did not correct for differences in the equivalency of colloid compared to crystalloid solutions. Some authorities suggest that the volume expansive of colloid exceed crystalloid on absolute volume basis (7). However, corrections would likely accentuate the differences in mortality seen with volume.

It had been proposed that colloid infusion might be protective of the lungs by retaining fluid in the vascular space by oncotic pressure. However, recent studies have suggested show that colloids do not lower lung water (8). Furthermore, a recent meta-analysis found no evidence trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery (9). Furthermore, the use of hydroxyethyl starch might increase mortality. Our study is consistent with these studies.

Our trial has certain limitations. First, our study was single center. Second, the design did not include hemodynamic monitoring or other therapies. How these confounding variables might have affected the results is unknown. Third, only 43 patients were included in the trial. The trial was underpowered and confirmation of the results will be needed by larger trials.

This study demonstrates that the initial volume of fluid administered has effects on outcomes in patients with ARDS. The data in this manuscript support a dry or conservative strategy for management of ARDS. Furthermore, the choice of fluid also affects outcomes. The data in this paper would recommend the maintenance of relatively stable blood pressure with low volumes of crystalloid. As colloids are not associated with an improvement in survival, are less readily available, and are more expensive than crystalloids, it is hard to see how their continued use in clinical practice can be justified.

Conflict of Interest

None of the authors declared a conflict of interest.

Acknowledgements

The concept of this research was built by Prof. Dr. Yong –Jie Yin and Dr Sanjaya Karki. However, most of the credit goes to Dr Jing Xiao Zhang in order to complete this research successfully. All the other co-authors have equally contributed.  

References

1. Matthay AM, Zimmerman AG. Acute lung injury and the acute respiratory distress syndrome. Am J Respir Cell Mol Biol. 2005;33(4),319-327. [CrossRef] [PubMed]
2. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2(7511):319-23. [CrossRef] [PubMed]
3. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-33. [CrossRef] [PubMed]
4. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354(24):2564-75. [CrossRef] [PubMed]
5. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med. 2012;367(2):124-34. [CrossRef] [PubMed]
6. Bellmann R, Feistritzer C, Wiedermann CJ. Effect of molecular weight and substitution on tissue uptake of hydroxyethyl starch: a meta-analysis of clinical studies. Clin Pharmacokinet 2012;51:225-36. [CrossRef] [PubMed]
7. The SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247-2256. [CrossRef] [PubMed]
8. van der Heijden M, Verheij J, van Nieuw Amerongen GP, Groeneveld AB. Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and nonseptic critically ill patients with hypovolemia. Crit Care Med. 2009;37(4):1275-81. [CrossRef]  [PubMed]
9. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013 Feb 28;2:CD000567. [CrossRef] [PubMed]

Reference as: Karki S, Yin Y-J, Zhang J-X, Samani N, Pradhan D, Deuja SS, Karki R, Thakur R, Zhao N. Fluid in the management of the acute respiratory distress syndrome. Southwest J Pulm Crit Care. 2013;6(6):289-98. doi: http://dx.doi.org/10.13175/swjpcc044-13 PDF