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Experience with high frequency oscillation ventilation during the 2009 H1N1 influenza pandemic in Australia and New Zealand.

During the 2009 H1N1 pandemic, large numbers of patients required complex and often prolonged mechanical ventilation (1). Conventional mechanical ventilation emphasising lung protection using low tidal volumes and high positive end expiratory pressure (PEEP) (2) was often inadequate to correct severe hypoxaemia. Even though previous literature suggests a mortality benefit with such an approach despite severe hypoxaemia (3), other modes of ventilation and salvage therapies including extracorporeal membrane oxygenation (ECMO) (4) and high frequency oscillation ventilation (HFOV) (5-8), were employed for the first time in many intensive care units (ICU) during the pandemic.

The ICU experience of the H1N1 pandemic in Australia and New Zealand (ANZ) has previously been reported (1), although the clinical progress of H1N1 patients requiring HFOV has not yet been extensively described (8). HFOV use in this setting represents a ventilatory strategy for severe respiratory failure in the absence of significant airway obstruction, whereby the mean airway pressure can be increased to approach the barotrauma limits of normal lung, to improve functional residual capacity and oxygenation. Ventilation is accomplished by using high frequencies around 3 to 6 Hz generated by a rapidly moving piston resulting in tidal volumes of 1 to 5 ml. This study examined the use of HFOV in ANZ during the 2009 H1N1 pandemic, with the aim of comparing clinical utilisation to the same period in the previous year.


All confirmed H1N1 positive patients admitted to 187 ICUs in ANZ during 2009 were prospectively identified as part of the Australian and New Zealand Intensive Care (ANZIC) Influenza Investigators registry (1) and the Australia and New Zealand ECMO Influenza study (4). All ICUs using HFOV were invited to participate in the present study. Data were extracted from the ANZIC Influenza Investigators registry (1) and additional data collected on a paper case report form. The study period spanned 1 June to 31 August 2009. Non-H1N1 patients were retrospectively identified as receiving HFOV in the same ICUs during the study period, and in the same time period in 2008. The 2008 cohort and patients without H1N1 in 2009 were included to investigate the patterns of usage of HFOV in ANZ prior to the H1N1 pandemic.

Demographic data included the presence of morbid obesity defined as a body mass index greater than 35 kg/[m.sup.2] or a clinical diagnosis where weight and height could not be measured, chronic lung disease, chronic obstructive airways disease, asthma, chronic heart failure or the presence of any Acute Physiology and Chronic Health Evaluation (APACHE) III comorbidity (9). Due to the differences between illness severity scoring systems in children and adults, only APACHE III comorbidities were recorded. Indications for HFOV and the use of adjunctive therapies for respiratory failure including the use of inhaled nitric oxide (iNO), inhaled prostacyclins (iPC), lung volume recruitment manoeuvres, prone positioning and ECMO, plus the use of renal replacement therapies prior to and during the use of HFOV were examined. Recruitment manoeuvres were defined as administration of 40 cm[H.sub.2]O of PEEP/continuous positive airway pressure using any technique for 30 seconds or more with the aim to improve oxygenation (10).

The acute lung injury (ALI) score (range 0 to 4) (11) and oxygenation index (OI) [100 X [Paw.sub.mean]/(Pa[O.sub.2]/ Fi[O.sub.2]) with [Paw.sub.mean] representing the mean airway pressure] (12) were used to assess lung injury severity at the commencement of HFOV. HFOV settings and arterial blood gases were assessed at 4, 8, 12, 24, 36 and 48 hours after commencement, then daily thereafter until HFOV was ceased. Barotrauma as a complication of HFOV was specifically assessed. For patients with several episodes of HFOV within the one admission, the episode with the worst initial OI was used to describe the therapy and clinical condition of the patient but the total HFOV period was recorded. The principal patient outcome was hospital survival and treating clinician determined cause of death. The duration of mechanical ventilation, HFOV, ICU and hospital stay, functional status at hospital discharge (ambulant or not) and a pulse oximetry reading (Sp[O.sub.2]) on room air just prior to discharge home were assessed.

The data collection tool used in the Australia and New Zealand ECMO Influenza study (4) was made available to the present study investigators facilitating similar data collection and definitions.

Each centre obtained further institutional ethics committee approval for the retrospective collection of additional data as a sub-study of the ANZIC Influenza investigation with written individual patient consent waived. The study was supported in part by an unrestricted grant from Carefusion Australia who were not involved with the study design, data collection, analysis or manuscript production.


Statistical analysis employed STATA statistical software version 9 (College Station, Texas, USA). No neonates were included in the study. Children were defined as less than 15 years of age. No assumptions were made for missing data and proportions adjusted for the number of patients with available data. ALI scores were calculated using the sum of sub-scores divided by the number of sub-scores available. Descriptive statistics were calculated for all study variables with data reported as means or medians with interquartile ranges for continuous data, percentages for categorical data and 95% confidence intervals (CI) where appropriate. Comparisons were made between H1N1 patients with the 2009 and 2008 non-H1N1 patients using a chi-square test, Fisher's exact test, analysis of variance, Kruskal-Wallis tests and non-parametric tests for trend, as appropriate. A two-sided P value of less than 0.05 was considered to indicate statistical significance.


Nine ICUs in ANZ where HFOV was available during 2009 participated in this study. All had used HFOV in the previous year. There were between one and three HFOV machines available for clinical care (usually one) in each unit. The principal high frequency oscillation ventilators available in ANZ at the time of the study were the Sensormedics HFOV 3100A for neonates and paediatrics and 3100B for adults. All units had previous experience in HFOV prior to the H1N1 pandemic. The ICUs also had operating protocols in place but guidelines for its application were guided by general principle approaches to severe respiratory failure using lung protective strategies. Complete data for non-H1N1 patients were not available from one paediatric and one adult ICU due to incomplete records. Two other paediatric ICUs where HFOV was available were unable to provide data.

Demographic and outcome data are summarised from the perspectives of the H1N1 cohort compared to non-H1N1 patients (Table 1) and adult compared to paediatric patients (Table 2). For the June to August period in 2009, 22 H1N1 patients (17 adults, five children) and 10 non-H1N1 patients (five adults, five children) received HFOV, while there were 18 patients (two adults, 16 children) in 2008. APACHE III comorbidity was less common in the H1N1 group (9% compared with 60%, P=0.005). Even outside of the pandemic, bacterial or viral pneumonia remained the principal indication for HFOV (56%). Nine patients including one child with H1N1 were morbidly obese. Height and weight were directly measured in 39% and 59% of patients respectively. As assessed by the number of chest X-ray quadrants with infiltrates (four compared with 2.5, P=0.04) and the ALI scores (3.5 compared to 2.7, P=0.007), the H1N1 patients had more severe lung disease than those receiving HFOV in the previous year. H1N1 patients also stayed in the ICU and hospital longer than non-H1N1 patients by 10 days (P=0.002) and 19 days (P=0.03) respectively.

The principal mode of mechanical ventilation prior to the commencement of HFOV was pressure control (78%, Table 3). H1N1 patients commenced HFOV from a higher PEEP, lower Fi[O.sub.2] and smaller tidal volumes. The H1N1 cohort also commenced HFOV after a longer period of invasive mechanical ventilation, and in particular 24 hours longer receiving peak airway pressures greater than 30 cm[H.sub.2]O despite a predominantly pressure control strategy.

The duration of HFOV use was longer in the 2008 cohort (3.7 compared to 5.5 days, P=0.03), predominantly due to longer ventilation times in children (4.5 days compared to 2.8 days, P=0.03). Prior to commencing HFOV, some form of hypoxaemia salvage therapy was used in 60% of patients, usage being more common in H1N1 patients (82% compared to 33% in the 2008 cohort, P=0.008). Surfactant therapy was not described.

Children were generally managed with lower initial airway pressures and pressure oscillations, but received higher ventilation frequencies and were more likely to have a cuff leak around the endotracheal tube (Table 4). Parameters of initial oxygenation were similar in both children and adults but the lung injury score was higher in adult patients. The lower airway pressures used in children may reflect a broader application of HFOV in this group prior to the pandemic. In H1N1 positive patients, this approach to the initial settings of HFOV was not significantly different when children and adults were compared, although the median mean airway pressures used were similar (28 cm[H.sub.2]O in children compared to 30 cm[H.sub.2]O in adults, P=0.18).

The pattern of improvement in oxygenation was similar in children and adults as well as the H1N1 patients compared to non-H1N1 patients. Considering all patients, the [P.sub.a][O.sub.2]/Fi[O.sub.2] ratio improved from 78 mmHg to 125 mmHg (P <0.001) by 18 hours and remained stable thereafter (P=0.51). The OI improved from 30 to 21 within four hours (P=0.001) and continued to improve to 16 by 12 hours (P=0.0001). The OI remained stable thereafter during the first four days (P=0.25). The use of salvage therapies also decreased during the initial 24 hours of HFOV (iNO 16 to seven patients, P=0.03 and iPC four to two patients, P=0.26). In the 14 patients receiving iNO without concurrent ECMO, the proportion of patients continuing to receive iNO after HFOV commencement were 72%, 64%, 64% and 57% at 24 hours, two, three and four days respectively, despite receiving a median Fi[O.sub.2] between 0.55 and 0.65. Three patients received iNO for more than five days.

The progress of patients after commencing HFOV is recorded in Table 5. Barotrauma was more common in the H1N1 patients (41% compared to 0% in the 2009 non-H1N1 patients and 22% in the 2008 cohort, P=0.049) with no overall difference between children and adults with H1N1 (26% compared to 25%, P=1.00). However, the frequency of barotrauma prior to and following the commencement of HFOV were similar when all patients were considered (12% compared to 14%, P=1.00). The barotrauma consisted of five pneumomediastina (three occurring after the commencement of HFOV), 11 pneumothoraces (six after the commencement of HFOV) and one other barotrauma (pneumatocele) Occurring after commencement of HFOV. The ICU mortality was not increased in patients who developed barotrauma at any stage during mechanical ventilation (P=0.50).

Seven patients received ECMO (14%), six with H1N1. Four (57%) received ECMO before and after the commencement of HFOV with HFOV used in one (14%) to wean from ECMO while two (29%) patients received ECMO as a salvage therapy due to persisting hypoxia during HFOV. Both these latter patients survived to hospital discharge. The median ALI scores were similar in patients who received HFOV alone to those who received ECMO (3 compared to 3, P=0.40). The survival of patients having adjunctive ECMO was similar to those receiving HFOV alone (65% compared to 71%, P=1.00).

Of the entire cohort, 66% survived to hospital discharge (77% in H1N1 compared to 61% in 2008 and 50% in the non-H1N1 2009 cohort P=0.27, Table 1). There were insufficient numbers to allow assessment of specific disease outcomes. Intractable respiratory failure was the cause for two of the five deaths (40%) in 2009 and three of eight deaths in 2008 (38%, P=0.43). Deaths however were more commonly due to cardiovascular insufficiency in children (38% compared to 0%, P=0.02). One patient in the non-H1N1 2009 group who was receiving ECMO died of an intracerebral haemorrhage. Most patients were ambulant at the time of hospital discharge (87% H1N1 and 92% non-H1N1, P=1.00).


The most appropriate strategy for severe respiratory failure remains controversial with only low tidal volume and high PEEP volume controlled approaches clearly proven in randomised controlled trials (2,3). Despite an approach of tolerating oxygen saturations less than 90% in patients who remain difficult to oxygenate, the risks of this are not clearly defined (13,14). As such, for patients who remain severely hypoxic, approaches such as ECMO (8) and HFOV (8) have been developed, although clearly still await rigorous proof of a mortality benefit.

While the role of HFOV in adults has been difficult to define (15,16), we have documented the multicentre experience across ANZ in both adults and children with this modality. HFOV was only available in nine of 187 ICUs within ANZ. In total, HFOV was used in 22 of a total of 722 H1N1 patients (3%) admitted to intensive care during the study period (1). The delayed use of HFOV may represent a conservative approach to the use of HFOV in the absence of clear benefit for the technique from randomised controlled trials, or its limited availability even in those experienced units participating in this study.

A recent meta-analysis of HFOV outcomes including eight trials noted considerable variability in the ventilatory strategies and adjunctive therapies prior to HFOV commencement (17). In pooling a heterogeneous population of patients with acute respiratory distress syndrome, HFOV was shown to be superior to conventional mechanical ventilation with a risk ratio of 0.77 (95% CI 0.61 to 0.98) with no clear differences in efficacy between children and adults. As in our study, the meta-analysis demonstrated that oxygenation was significantly improved within the first 24 hours and remained higher than that of conventional ventilation by 16 to 24% for the first three days of HFOV. In our study, the maximal decrease in the OI occurred by eight hours following the commencement of HFOV. Of interest, the meta-analysis did not demonstrate a difference in OI between conventional ventilation and HFOV (17).

The differences in the initial HFOV parameters largely reflect differences in disease severity and recommendations for frequency based upon a higher resonate frequency in paediatric lungs (18,19). We found that barotrauma after the institution of HFOV in the H1N1 group was 41% being higher than the experience in 2008. Only one patient with barotrauma died, although the cause of death was not directly attributed to this. The meta-analysis of Sud found that barotrauma was not increased with HFOV (risk ratio 0.68, 95% CI 0.37 to 1.22), complicating some 11% of patients (17). The high rate of barotrauma in the H1N1 patients included in this study may be the result of the greater severity of lung disease or prolonged periods of high pressure ventilation prior to commencing HFOV. However, like Sud, we did not find an increase in barotrauma following the commencement of HFOV (17).

Three of the only four units with both HFOV and ECMO resources at the same centre applied both strategies in the same patient. In those units, the proportion of HFOV patients also receiving ECMO were 7%, 60% and 100%. ECMO retrieval services were not readily available on a national basis at the time of the pandemic. This emphasises that even in tertiary units, comprehensive management options were not universally available for severe respiratory failure. Salvage therapies in addition to HFOV including ECMO were not systematically applied, perhaps reflecting the paucity of evidence for mortality benefit (20-23). We confirmed that expensive adjunctive salvage therapies such as iNO remained in place despite the initiation of HFOV (8). In one North American tertiary centre, 26% of H1N1 patients were admitted to intensive care and of these 36% received either HFOV or ECMO as a salvage therapy (8). Other salvage therapies were also used but their administration protocols were not defined. Evidence-based strategies for the use of salvage therapies for severe respiratory failure at present remain elusive.

Table 6 details the summarised results of the ECMO and HFOV experience within ANZ during the H1N1 pandemic (4). Where HFOV was used in some 3% of H1N1 patients in the study period, ECMO was provided to 68 patients (9%). This probably reflects limited HFOV availability, with most ECMO centres not having a HFOV capability. Although similar ALI scores were found in ECMO and HFOV patients, the ECMO group was perhaps more severely ill, requiring higher airway pressures and having a lower [P.sub.a][O.sub.2]/Fi[O.sub.2] ratio. However, overall survival rates were similar, recognising the censoring of data in the ECMO series. Importantly, in the ECMO series, HFOV was reported in three patients prior to initiating ECMO. They are included in this study. A direct randomised controlled trial to compare ECMO and HFOV in acute respiratory distress syndrome has not been performed. The lack of a uniform approach to the application of adjunctive salvage therapies limits a direct outcome comparison of ECMO and HFOV from the Australian H1N1 experience (4). Overall, survival rates were similar for HFOV and ECMO (77% compared to 71% respectively).

Only two patients in the HFOV cohort required salvage therapy with ECMO for severe hypoxaemia. In the remaining patients receiving both therapies, HFOV was presumably used for 'lung-rest' or to wean from ECMO. Similar survival with HFOV (75%) and ECMO (71%) in the management of H1N1 has been reported from a single centre in North America, although the numbers treated were less than in the present study (8). We do not have comparable data on morbidity related to the differing techniques of ECMO and HFOV. A principal cause of mortality in ECMO is haemorrhage, explaining some 60% of the deaths which is not reported to be increased in HFOV patients. Pneumothorax rates prior to commencing ECMO and HFOV for H1N1 are similar (around 15%) which is not increased after initiating HFOV and would not be expected to be increased after ECMO (4). Intractable respiratory failure was reported as a cause of death in 30% of ECMO patients and represents 40% of HFOV patients.


This study describes the use of HFOV across two comparable time periods. Although H1N1 patient data were prospectively collected and all data was uncensored, interpretation is limited by the retrospective nature of the additional data. The data collected were comparable to those of the Australia and New Zealand Influenza ECMO study (4). HFOV was an uncommonly used technique in ANZ prior to the H1N1 pandemic. As the majority of the non-H1N1 group comprises children, direct physiologic and ventilator setting are not comparable between the H1N1 and non-H1N1 groups. It does however, provide an insight into HFOV use and description of general outcomes. Despite incomplete non-H1N1 records from two units, to the best of our knowledge the data for the 2009 winter are complete. The general lack of availability of HFOV outside of paediatric ICUs at the time is highlighted. We cannot make comment on the potential patient outcomes if they had not received HFOV due to the descriptive nature of the study. However, our study hospital survival rate of 77% in H1N1 patients compares favourably with previous reports with survival around 61% (17).


Our study found HFOV was used infrequently in the H1N1 pandemic. Prior to the pandemic, HFOV was used mostly in children. HFOV improved oxygenation in severe respiratory failure when conventional ventilation has been ineffective with an overall survival was similar to patients receiving ECMO (1,4,17). HFOV, being less invasive and requiring fewer resources than extracorporeal techniques, has the potential to be applied in more ICUs, but should not be considered a substitute for ECMO. The use of adjunctive therapies such as iNO, iPC and prone ventilation when other modalities such as HFOV are available remains uncertain. Head-to-head trials continue to be needed to define a stepwise approach to the support of such patients based upon evidence of benefit, cost and local applicability.


The ANZIC Influenza Investigators is a collaboration of the Australia and New Zealand Intensive Care Society Society Clinical Trials Group, the ANZIC Research Centre, the Australasian Society of Infectious Diseases Clinical Trials Group, the Paediatric Study Group of the ANZIC Society and the ANZIC Society Centre for Outcome and Resource Evaluation. We also express our thanks to the Australia and New Zealand ECMO Influenza Investigators for providing the case report form to assist with data collection, Belinda Howe, Project Manager at the ANZIC Research Centre for cross referencing data and Dr Alan Duncan for contributing paediatric data from the Paediatric Intensive Care Unit of Western Australia. We thank Dr Andrew Udy for his assistance in preparation of the manuscript.


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R. J. BOOTS *, J. LIPMAN ([dagger]), M. LASSIG-SMITH ([double dagger]), D. P. STEPHENS ([section]), J. THOMAS **, Y. SHEHABI ([dagger][dagger]), F. BASS ([double dagger][double dagger]), A. ANTHONY ([section][section]), D. LONG ***, I. M. SEPPELT ([dagger][dagger][dagger]), L. WEISBRODT ([double dagger][double dagger][double dagger]), S. ERICKSON ([section][section][section]), J. BECA ****, C. SHERRING ([dagger][dagger][dagger][dagger]), S. McGUINESSHH ([double dagger][double dagger]) ([double dagger][double dagger]), R. PARKE ([section][section][section][section]) E. R. STACHOWSKI *****, R. BOYD ([dagger][dagger][dagger][dagger][dagger]), B. HOWE ([double dagger][double dagger][double dagger][double dagger][double dagger])

Multicentre in Australia and New Zealand

* M.B., B.S. (Hons), Ph.D., F.R.A.C.P., F.C.I.C.M., G.Dip.Clin.Epi., M.Med.Sci., M. Health Admin., Info. Tech., Deputy Director, Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital and Associate Professor, Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland.

([dagger]) F.F.A. (S.A.), F.F.A. (Critical Care S.A.), F.C.I.C.M., M.D., Professor, Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital and Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland.

([double dagger]) M.N. (Critical Care), Research Co-ordinator, Department of Intensive CareMedicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland.

([section]) F.A.N.Z.C.A., F.C.I.C.M., Associate Professor and Director, Department of Intensive Care Services, Royal Darwin Hospital, Darwin, Northern Territory.

** B.N., G.Dip. (Public Health), Research Co-ordinator, Department of Intensive Care Services, Royal Darwin Hospital, Darwin, Northern Territory.

([dagger][dagger]) F.C.I.C.M., E.M.B.A., Associate Professor and Director, Intensive Care Unit, Prince of Wales Hospital, Sydney, New South Wales.

([double dagger][double dagger]) B.N., Research Co-ordinator, Intensive Care Unit, Prince of Wales Hospital, Sydney, New South Wales.

([section][section]) F.R.A.C.P., F.C.I.C.M., Associate Professor and Director, Royal Children's Hospital, Brisbane, Queensland.

*** M.N., Research Co-ordinator, Royal Children's Hospital, Brisbane, Queensland.

([dagger][dagger][dagger]) F.A.N.Z.C.A., F.C.I.C.M., Associate Professor and Senior Staff Specialist, Department of Intensive Care Medicine Nepean Hospital, Penrith and Sydney Medical School, Nepean, University of Sydney, Sydney, New South Wales.

([double dagger][double dagger][double dagger]) M.N. (Hons), Research Co-ordinator, Department of Intensive Care Medicine, Nepean Hospital, Penrith and Sydney Medical School Nepean, University of Sydney, New South Wales.

([section][section][section]) F.R.A.C.P., F.C.I.C.M., Senior Staff Specialist, Paediatric Intensive Care Unit, Perth, Western Australia.

**** FC.I.C.M., F.R.A.C.P., Senior Staff Specialist, Paediatric Intensive Care Unit, Starship Children's Hospital, Auckland, New Zealand.

([dagger][dagger][dagger][dagger]) G.Dip. (Advanced Nursing Science), Research Co-ordinator, Paediatric Intensive Care Unit, Starship Children's Hospital, Auckland, New Zealand.

([double dagger][double dagger][double dagger][double dagger]) M.B., C.H.B., F.C.I.C.M., Senior Staff Specialist, Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, New Zealand.

([section][section][section][section]) M.H.S.C. (Hons), Research Co-ordinator, Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, New Zealand.

***** F.A.N.Z.C.A., F.C.I.C.M., Associate Professor and Director, Intensive Care Unit, Westmead Hospital, Westmead, New South Wales.

([dagger][dagger][dagger][dagger][dagger]) R.N., Research Co-ordinator, Intensive Care Unit, Westmead Hospital, Westmead, New South Wales.

([double dagger][double dagger][double dagger][double dagger][double dagger][double dagger]) R.N., Research Fellow, Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria.

Address for correspondence: Dr R. Boots, Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, Qld 4029.

Accepted for publication on May 24, 2011.
Table 1
Patient demographics

 Non H1N1
 H1N1, n=22 2009, n=10

 Median Median
 (IQR)/n (%) (IQR)/n (%)

Age, y 31 (7-43) 19 (0.6-55)
Male 8 (36) 7 (70)
Children <15 y 5 (23) 5 (50)
APACHE III comorbidity 6 (60)
Chronic lung disease 5 (23) 4 (40)
Morbid obesity 9 (41) 1 (10)
 Aspiration 1 (5) 8 (80)
 Non-pulmonary ARDS 21(95) 2 (20)
 Bacterial/viral pneumonia -- --
 Other pulmonary disease -- --
Inotrope/vasopressor use 11 (50) 6 (60)
Renal replacement therapy
 Prior HFOV only 1 (5) 1 (10)
 Post HFOV only 4 (18) 0 (0)
 Pre and post HFOV 3(14) 1 (10)
Quadrants on CXR 4 (3-4) 3.5 (2-4)
ALI score 3.5 (3-3.7) 2.7 (2.7-3.7)
ICU length of stay, days 25 (17-36) 11.5 (3-19)
Hospital length of stay, days 41 (25-63) 22 (3-33)
 Died ICU 5 (23) 5 (50)
 Survived hospital 17 (77) 5 (50)
Ambulant at hospital discharge 14 (87), n=16, 4 (80), n=5
Discharge Sp[O.sub.2] 96 (95-97), n=13 97.5 (97-98), n=2

 ALL 2008,
 n = 18 Total, n=50

 Median Median
 (IQR)/n (%) (IQR)/n (%)

Age, y 1.2 (0.5-12) 14 (0.8-37)
Male 11 (61) 26 (52)
Children <15 y 16 (89) 26 (52)
APACHE III comorbidity 7 (40) 15 (30)
Chronic lung disease 5 (28) 16 (32)
Morbid obesity 1 (6) 11 (22)
 Aspiration 1 (6) 1 (2)
 Non-pulmonary ARDS 3 (17) 4 (8)
 Bacterial/viral pneumonia 10 (56) 39 (78)
 Other pulmonary disease 4 (22) 6 (12)
Inotrope/vasopressor use 10 (56) 27 (54)
Renal replacement therapy
 Prior HFOV only 0 (0) 2 (4)
 Post HFOV only 3 (17) 7 (14)
 Pre and post HFOV 0 (0) 4 (8)
Quadrants on CXR 2.5 (2-4) 4 (3-4)
ALI score 2.7 (2-3) 3 (2.7-3.7)
ICU length of stay, days 15 (11-22) 19 (10.27)
Hospital length of stay, days 22 (17-36) 26 (18-48)
 Died ICU 7 (39) 17 (34)
 Survived hospital 11 (61) 33 (66)
Ambulant at hospital discharge 8 (89), n=9 26 (90), n=29
Discharge Sp[O.sub.2] 98.5 (97-100), n=4 97 (95-98), n=19


Age, y 0.004
Male 0.15
Children <15 y 0.001
APACHE III comorbidity 0.006
Chronic lung disease 0.60
Morbid obesity 0.02
Indication 0.02
 Non-pulmonary ARDS
 Bacterial/viral pneumonia
 Other pulmonary disease
Inotrope/vasopressor use 0.87
Renal replacement therapy 0.32
 Prior HFOV only
 Post HFOV only
 Pre and post HFOV
Quadrants on CXR 0.04
ALI score 0.007
ICU length of stay, days 0.002
Hospital length of stay, days 0.03
Outcome 0.27
 Died ICU
 Survived hospital
Ambulant at hospital discharge 1.00
Discharge Sp[O.sub.2] 0.08

* All comparisons H1N1 versus non-H1N1 2009 versus ALL 2008.
IQR=interquartile range, APACHE=Acute Physiology and Chronic Health
Evaluation, ARDS=acute respiratory distress syndrome, HFOV=high
frequency oscillation ventilation, CXR=chest X-ray, ALI=acute lung
injury, ICU=intensive care unit, Sp[O.sub.2]=oxygen saturation by
pulse oximetry.

Cohort comparison of adults and children receiving HFOV

 (<15 years),
 Adult, n=24 n=26

 Median Median
 (IQR)/n (%) (IQR)/n (%)

Age, y 37 (28-53) 0.9 (0.5-2.7)
Male 13 (54) 13 (50)
 2009 22 (91) 10 (38)
 2008 2 (8) 16 (61)
APACHE III comorbidity 3 (13) 12 (46)
Chronic lung disease 3 (13) 11 (42)
Morbid obesity 9 (38) 2 (8)
 H1N1 17 (71) 5 (19)
 Other bacterial/viral 5 (21) 13 (50)
 Aspiration 0 (0) 1 (4)
 Non-pulmonary ARDS 1 (4) 2 (8)
 Other pulmonary disease 1 (4) 5 (19)
Inotrope/vasopressor use 13 (54) 14 (54)
Renal replacement therapy 11 (45) 2 (8)
Quadrants on CXR 4 (3-4) 3 (2-4)
ALI score 3.7 (3.2-3.7) 2.7 (2.3-3)
 Pre HFOV only 1 (4) 0 (0)
 Post HFOV only 2 (8) 0 (0)
 Pre and post HFOV 3 (13) 1 (4)
Prior iPC use 4 (17) 0 (0)
Prior iNO use 6 (25) 9 (35)
Time to commence HFOV from 4.1 (0.7-11) 4.1 (0.3-7.9)
ICU admission, days
ICU length of stay, days 22.5 (5-33) 16 (13-22)
Hospital length of stay, days 25.5 (12-48) 29 (19-45)
 Died ICU 10 (42) 7 (26)
 Survived hospital 14 (58) 18 (69)
Ambulant at hospital discharge 12 (86), n = 14 14 (93), n=15
Discharge Sp[O.sub.2] 96 (95-97), n=11 98 (96-95), n=8

 Total, n=50 P

 (IQR)/n (%)

Age, y 14 (0.8-37) 0.001
Male 26 (52) 0.78
Cohort <0.001
 2009 32 (64)
 2008 18 (36)
APACHE III comorbidity 15 (30) 0.01
Chronic lung disease 14 (28) 0.03
Morbid obesity 11 (22) 0.02
Indication 0.002
 H1N1 22 (44)
 Other bacterial/viral 18 (36)
 Aspiration 1 (2)
 Non-pulmonary ARDS 3 (6)
 Other pulmonary disease 6 (12)
Inotrope/vasopressor use 27 (54) 1.00
Renal replacement therapy 13 (26) 0.003
Quadrants on CXR 4 (2-4) 0.05
ALI score 3 (2.7-3.7) 0.001
ECMO 0.13
 Pre HFOV only 1 (2)
 Post HFOV only 2 (2)
 Pre and post HFOV 4 (8)
Prior iPC use 4 (8) 0.05
Prior iNO use 15 (30) 0.54
Time to commence HFOV from 4.1 (0.3-8.3) 0.61
ICU admission, days
ICU length of stay, days 19 (10-27) 0.39
Hospital length of stay, days 26 (18-48) 0.62
 Died ICU 17 (34) 0.37
 Survived hospital 32 (64) 0.56
Ambulant at hospital discharge 26 (90), n=29 0.60
Discharge Sp[O.sub.2] 97 (95-98), n=19 0.16

HFOV=high frequency oscillation ventilation, IQR=interquartile range,
APACHE=Acute Physiology and Chronic Health Evaluation, ARDS=acute
respiratory distress syndrome, CXR=chest X-ray, ALI=acute lung injury,
ECMO=extracorporeal membrane oxygenation, iPC=inhaled prostacyclins,
iNO=inhaled nitric oxide, ICU=intensive care unit, Sp[O.sub.2]=oxygen
saturation by pulse oximetry.

Mechanical ventilation prior to the commencement of HFOV

 H1N1, n=22 2009, n = 10

 Median Median
 (IQR)/n (%) (IQR)/n (%)

Ventilation mode
 Pressure control 17 (77) 9 (90)
 Volume control 4 (18) 1 (10)
 PRVC 1 (5)
Fi[O.sub.2] 0.8 (0.7-1) 1.0 (0.9-1.0)
Pa[O.sub.2] mmHg 67 (61-79) 68 (57-90)
Pa[O.sub.2]/Fi[O.sub.2] 81 (67-111) 85.5 (64-94)
Respiratory rate 22 (19-26) 22 (17-30)
PEEP, cm[H.sub.2]O 15 (11-17) 12.25 (10-14)
[P.sub.Peak] cm[H.sub.2]O 30 (28-36) 28 (28-34)
Tidal volume, ml/kg ** 4.4 (1.6-5.1) 5.5 (3.6-8.6)
Time [P.sub.peak] >30 0.9 (0.35-3.6) 0 (0-0.125)
cm[H.sub.2]O, days
Time Fi[O.sub.2] >0.8, 0.25 (0-1) 0.23 (0.04-0.38)
Invasive ventilation, days 4.9 (2-10) 1.4 (0.38-6)
Non-invasive ventilation, 0.35 (0.2-0.9), n=4 0.58, n=1
iNO 8 (36) 2 (20)
iPC 4 (18) 0 (0)
Prone positioning 9 (41) 4 (40)
Documented recruitment 5 (22) 0 (0)
ECMO 6 (27) 1 (10)
Any salvage *** 18 (82) 6 (60)

 ALL 2008, n=18 Total N=50

 Median Median
 (IQR)/n (%) (IQR)/n (%)

Ventilation mode
 Pressure control 13 (72) 39 (78)
 Volume control 5 (28) 10 (20)
 PRVC 1 (2)
Fi[O.sub.2] 1 (0.8-1) 0.95 (0.7-1)
Pa[O.sub.2] mmHg 58 (43-75) 64 (53-79)
Pa[O.sub.2]/Fi[O.sub.2] 70 (49-94) 81 (61-107)
Respiratory rate 25 (24-31) 23 (20-27)
PEEP, cm[H.sub.2]O 10 (8-14) 12 (9-15)
[P.sub.Peak] cm[H.sub.2]O 30.5 (28-33) 30 (28-34)
Tidal volume, ml/kg ** 5.8 (4.7-7.4) 4.9 (3.3-6.6)
Time [P.sub.peak] >30 0.25 (0-0.5) 0.45 (0-1)
cm[H.sub.2]O, days
Time Fi[O.sub.2] >0.8, 0.5 (0-0.8) 0.3 (0-0.8)
Invasive ventilation, days 0.75 (0.5-5.3) 2.1 (0.5-6.5)
Non-invasive ventilation, 1 (0.5-1.4), n=6 0.58 (0.2-1.3), n=11
iNO 5 (28) 15 (30)
iPC 0 (0) 4 (8)
Prone positioning 1 (6) 14 (28)
Documented recruitment 1 (6) 6 (12)
ECMO 0 (0) 7 (14)
Any salvage *** 6 (33) 30 (60)

 P *

Ventilation mode 0.78
 Pressure control
 Volume control
Fi[O.sub.2] 0.03
Pa[O.sub.2] mmHg 0.28
Pa[O.sub.2]/Fi[O.sub.2] 0.33
Respiratory rate 0.15
PEEP, cm[H.sub.2]O 0.08
[P.sub.Peak] cm[H.sub.2]O 0.77
Tidal volume, ml/kg ** 0.03
Time [P.sub.peak] >30 0.01
cm[H.sub.2]O, days
Time Fi[O.sub.2] >0.8, 0.76
Invasive ventilation, days 0.04
Non-invasive ventilation, 0.56
iNO 0.75
iPC 0.10
Prone positioning 0.02
Documented recruitment 0.15
ECMO 0.04
Any salvage *** 0.008

* All comparisons H1N1 versus non-H1N1 2009 versus ALL 2008. **
Combined actual body weight (estimated and measured combined).

*** Any salvage=iNO or iPC or prone positioning or recruitment
manoeuvres. HFOV=high frequency oscillation ventilation,

IQR=interquartile range, PRVC=pressure regulated volume control,
PEEP=positive end expiratory pressure, [P.sub.Peak]=peak airway
pressure, iNO= inhaled nitric oxide, iPC=inhaled prostacyclins,
ECMO=extracorporeal membrane oxygenation.

Initial parameters used in establishing HFOV

 Adults, n=22 Children, n=28

 Median Median
 (IQR)/n (%) (IQR)/n (%)

[Paw.sub.mean], cm[H.sub.2]O 30 (26-36) 26 (24-30)
Frequency, Hz 6 (5-6) 10 (8-11)
[DELTA]P, cm[H.sub.2]O 68 (55-84) 47 (43-55)
Fi[O.sub.2] 1 (0.75-1) 0.9 (0.6-1)
Pa[O.sub.2]/Fi[O.sub.2], mmHg 81 (64-103) 68 (57-107)
Oxygenation index, cm[H.sub.2]O/mmHg 30 (20-40) 29 (20-30)
Lung injury score 3.7 (3.2-3.7) 2.7 (2.3-3.3)
Cuff leak, any time during HFOV 5 (23) 16 (57)

 Total, n=50 P

 (IQR)/n (%)

[Paw.sub.mean], cm[H.sub.2]O 28 (25-34) 0.007
Frequency, Hz 7 (6-10) 0.001
[DELTA]P, cm[H.sub.2]O 55 (46-70) 0.002
Fi[O.sub.2] 0.95 (0.6-1) 0.60
Pa[O.sub.2]/Fi[O.sub.2], mmHg 78 (60-107) 0.27
Oxygenation index, cm[H.sub.2]O/mmHg 30 (20-40) 0.63
Lung injury score 3 (2.7-3.7) 0.001
Cuff leak, any time during HFOV 21 (42) 0.02

HFOV=high frequency oscillation ventilation, IQR=interquartile range,
[Paw.sub.mean]=mean airway pressure.

Ventilation progress following initiation of HFOV

 H1N1, n=22 NHN 2009, n=10

 Median Median
 (IQR)/n (%) (IQR)/n (%)

HFOV duration, days 3.7 (2.0-5.2) 2.5 (1.2-3.9)
Prone positioning 8 (36) 5 (56)
Recruitment manoeuvre 1 (5) 0 (0)
 Pre HFOV only 1 (5) 0 (0)
 Post HFOV only 2 (9) 0 (0)
 Pre and post HFOV 3 (14) 1 (10)
 Pre HFOV 3 (14) 0 (0)
 Post HFOV 4 (18) 0 (0)
Patients with
 Pre HFOV 2 (10) 0 (0)
 Post HFOV 3 (14) 0 (0)
Other barotrauma **
 Pre HFOV 0 (0) 0 (0)
 Post HFOV 1 (5) 0 (0)

 ALL 2008, n=18 Total, n=50 P *

 Median Median
 (IQR)/n (%) (IQR)/n (%)

HFOV duration, days 5.5 (3.1-7.9) 3.72 (1.8-5.6) 0.03
Prone positioning 3 (17) 16 (32) 0.17
Recruitment manoeuvre 0 (0) 1 (2) 1.00
ECMO 0.27
 Pre HFOV only 0 (0) 1 (2)
 Post HFOV only 0 (0) 2 (4)
 Pre and post HFOV 0 (0) 4 (8)
Pneumothorax 0.50
 Pre HFOV 2 (11) 5 (10)
 Post HFOV 2 (11) 6 (12)
Patients with 0.17
 Pre HFOV 0 (0) 2 (4)
 Post HFOV 0 (0) 3 (6)
Other barotrauma ** 1.00
 Pre HFOV 0 (0) 0 (0)
 Post HFOV 0 (0) 1 (0.2)

* All comparisons H1N1 versus non-H1N1 2009 versus ALL 2008. ** Other
barotraumas=pneumatoceles, arterial gas embolism from a pul-monary
origin. HFOV=high frequency oscillation ventilation, IQR=interquartile
range, ECMO=extracorporeal membrane oxygenation.

Comparison of HFOV cohort to ECMO in Australian and New Zealand H1N1
pandemic (4)

 ECMO cohort, n=68 HFOV cohort, n=22
 Median (IQR)/n (%) Median (IQR)/n (%)

CXR quadrants 4(4-4) 4 (3.5-4)
ALI score 3.8 (3.5-4) 3.3 (3-3.7)
[P.sub.a][O.sub.2]/ 56 (48-63) 81 (51-104)
Prior conventional 5.6 (4.6-6.7) 4 (2.5-5.2)
ventilation volume, ml/kg
PEEP, cm[H.sub.2]O 18 (15-20) 15 (12-18)
PeakPaw, cm[H.sub.2]O 36 (33-38) 32 (28-36)
Hypoxaemia salvage
 iNO 20 (32) 8 (36)
 iPC 14 (22) 4 (18)
 Prone positioning 12 (20) 11 (50)
 Recruitment manoeuvre 38 (67) 5 (23)
Survival at ICU discharge 48 (71) 17 (77)

HFOV=high frequency oscillation ventilation, ECMO=extracorporeal
membrane oxygenation, IQR=interquartile range, CXR=chest X-ray,
ALI=acute lung injury, PEEP=positive end expiratory pressure,
iNO=inhaled nitric oxide, iPC=inhaled prostacyclins, ICU=intensive
care unit.
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Title Annotation:Original Papers
Author:Boots, R.J.; Lipman, J.; Lassig-Smith, M.; Stephens, D.P.; Thomas, J.; Shehabi, Y.; Bass, F.; Anthon
Publication:Anaesthesia and Intensive Care
Geographic Code:8NEWZ
Date:Sep 1, 2011
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