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Current oxygenation practice in ventilated patients--an observational cohort study.

SUMMARY

Oxygen therapy is a mainstay of critical care medicine, yet its optimal therapeutic use has not been systematically evaluated. A detailed understanding of current practice in oxygen therapy in intensive care is required to enable future interventional studies. We aimed to describe current oxygenation practice in patients requiring [greater than or equal to] 48 hours of mechanical ventilation (MV) at an academic tertiary referral centre.

We collected longitudinal arterial blood gas and hourly oxygenation data from intensive care unit charts in a consecutive cohort of 40 trauma, 41 medical and 20 surgical patients for their first seven MV days, analysed data for 14,063 MV hours, and derived time-weighted averages (TWA) of variables for each 24-hour interval on MV for all patients.

The TWA-Fi[O.sub.2] was 0.42 (95% CI 0.41 to 0.44) and TWA-Sp[O.sub.2] was 97.1% (95% CI 96.8 to 97.4) for the first seven MV days. TWA-Pa[O.sub.2] was >80 mmHg on 80% of MV days. TWA-Fi[O.sub.2] of [greater than or equal to] 0.35 was used to achieve TWA-Sp[O.sub.2] >95% on 61% of MV days. Of 58 MV days with TWA-Fi[O.sub.2] [greater than or equal to] 0.60, TWA- Sp[O.sub.2] [greater than or equal to] 96% occurred on 28 (48%) days. Mean Sp[O.sub.2] and Pa[O.sub.2] in patients with severe acute lung injury (ALI) scores were higher than recommended targets. Wide variability in the mean Sp[O.sub.2] and Pa[O.sub.2] was observed in patients with comparable ALI scores.

Inspired oxygen therapy in these MV patients was 'liberal', with Pa[O.sub.2] and Sp[O.sub.2] values generally above 80 mmHg and 96% respectively. An interventional study comparing current practice to more conservative targets (Pa[O.sub.2] [approximately equal to] 60 to 65 mmHg and/or Sp[O.sub.2] [approximately equal to] 90 to 92%) appears possible.

Key Words: intensive care, mechanical ventilation, oxygen inhalation therapy, time-weighted average (TWA), acute lung injury (ALI)

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Oxygen ([O.sub.2]) is a life-saving drug and is used ubiquitously in hospitals and intensive care units (ICU) worldwide. International consensus opinion on mechanical ventilation (MV) proposed using an inspired [O.sub.2] concentration (Fi[O.sub.2]) necessary to achieve at least 90% Sa[O.sub.2] (arterial [O.sub.2] saturation) as an acceptable target for most applications of ventilatory support (1). Nevertheless, besides few specific clinical conditions (2-5), there is little or no evidence to guide ICU clinicians on titration of [O.sub.2] therapy. Furthermore, there is uncertainty about optimal arterial [O.sub.2] saturation (Sp[O.sub.2]) and tension (Pa[O.sub.2]) targets for [O.sub.2] therapy.

In a retrospective database study, hyperoxia was frequently present in Dutch ICU patients but usually did not lead to adjustment of ventilator settings (6). A recent study reported common use of liberal [O.sub.2] supplementation in ventilated patients with acute lung injury (ALI) and showed a correlation between exposure to excessive Fi[O.sub.2] and worsening of oxygenation index in a dose response manner (7). In a post hoc analysis, high Fi[O.sub.2] was associated with higher mortality even after controlling for Pa[O.sub.2]/ Fi[O.sub.2] (8). There is no strong evidence that targeting higher levels of Sp[O.sub.2] or Pa[O.sub.2] within the acceptable range is more advantageous. On the other hand, limits of hypoxia tolerance are not well defined.

Our hypothesis for this study was that in routine care during MV, patients spend long periods of time with more than necessary oxygenation levels (Sp[O.sub.2], Sa[O.sub.2], Pa[O.sub.2] and Fi[O.sub.2]). At present, the longitudinal data on actual oxygenation practice outside of clinical trial setting is scarce; in particular, the data on mean oxygenation levels over a longer period of ventilation is non-existent. Ascertaining the current practice and pattern of [O.sub.2] therapy in detail may help design an interventional study. Accordingly, we investigated our current practice concerning oxygenation (Sp[O.sub.2], Sa[O.sub.2] and Pa[O.sub.2]) and use of Fi[O.sub.2] in patients requiring MV for [greater than or equal to] 48 hours in an academic tertiary care ICU in Melbourne, Australia. In addition to the main aim of describing longitudinal practice of [O.sub.2] therapy, our secondary objective was to determine if oxygenation practice differs significantly among patients with different ALI scores.

METHODS

We conducted an observational cohort study of 101 patients admitted between May 2010 and June 2011 in a mixed medical and surgical 45-bed ICU at a university-affiliated tertiary care hospital in Melbourne, Australia. The hospital ethics committee approved this study (approval number 29/11) and waived the requirement for informed consent. Eligible patients requiring [greater than or equal to] 48 hours of MV were identified from the prospective ICU database. We excluded patients if they were either considered at risk for imminent death by the treating medical team, diagnosed with conditions where higher or lower [O.sub.2] levels are potentially contraindicated such as severe chronic obstructive pulmonary disease or carbon monoxide poisoning, or required extracorporeal membrane oxygenation or hyperbaric [O.sub.2] therapy, or transferred on MV from another ICU.

We recorded patient-related variables (demographics, admission diagnosis, Charlson's comorbidity score (9), illness severity scores (10-12), worst lactate, pH range), process-of-care-related variables (Fi[O.sub.2], positive end-expiratory pressure [PEEP], co-oximeter measured Sa[O.sub.2], Pa[O.sub.2], Sp[O.sub.2], hours spent in pre-specified Fi[O.sub.2] and Sp[O.sub.2] ranges, and time spent at Pa[O.sub.2] >100 mmHg and Pa[O.sub.2] >200 mmHg), and outcome-related variables (change ([DELTA]) in Pa[O.sub.2]/ Fi[O.sub.2] from day 0 to day 3 or day 6, and in-hospital mortality) for all patients. We longitudinally collected hourly data for key oxygenation-related variables during the first seven days of invasive MV. We recorded all arterial blood gases (ABG) and derived a 24-hour time-weighted mean Pa[O.sub.2] for the first four days and the seventh day of MV. In addition, the 24-hour time-weighted mean Sa[O.sub.2] was derived for the first three days. Since the upper limits of the target range for Sp[O.sub.2] and Pa[O.sub.2] in major clinical trials of patients with ALI/acute respiratory distress syndrome (13,14) were 95% and 80 mmHg respectively, oxygenation above these limits was considered as 'liberal'.

Time-weighted averages (TWA) of the variables-of-interest were derived for each 24-hour interval of MV for all patients. The TWA was calculated as the sum-product of values of variable-of-interest and their duration intervals divided by sum of all intervals i.e., TWA(X) = [summation] [t.sub.n][X.sub.n]/[summation] [t.sub.n]; where [t.sub.n] is the duration of the nth interval, [X.sub.n] is the variable-of-interest level during the nth interval, and sum total of such intervals ([summation], [t.sub.n]) is equal to the time period for which TWA is calculated. The time-interval for variables recorded from ICU observation charts was one hour as the bedside nurse recorded clinical data every hour, whereas time-interval for variables recorded from ABG was calculated as the time-difference before the next ABG. We did not include days where less than 12 hours of data was available (e.g. if patient was extubated or died). We classified patients a priori into three groups based on the severity of their ALI scores on day 0. Oxygenation-related parameters were then compared among these groups. Sequential Organ Failure Assessment (11) and ALI scores (12) were calculated after data collection for the entire study was completed. The Sequential Organ Failure Assessment scores reported in the study exclude the Glasgow coma scale component. ALI scores were calculated as an average of scores across 24-hour TWA Pa[O.sub.2]/Fi[O.sub.2] ([greater than or equal to] 300=0, 225-299=1, 175-224=2, 100-174=3, <100=4), chest X-ray (1 point per quadrant with infiltrate) and 24hour TWA PEEP in cm[H.sub.2]O ([less than or equal to] 5=0, 6-8=1, 9-11=2, 12-14=3, [greater than or equal to] 15=4) for that day. ALI scores <1, 1 to 2.5 and >2.5 identified mild, moderate and severe respiratory failure respectively. The number of quadrants showing infiltrates on chest X-rays were recorded after agreement between two investigators.

Statistical analysis

We aimed to study a convenience sample of at least 100 patients, as such a sample was anticipated to provide a sufficient representation of the unit practice. For patients who were readmitted to the ICU and required MV [greater than or equal to] 48 hours, only the index admission was considered. All analysis was performed using SAS version 9.2 (SAS Institute Inc., Cary, NC, USA). Variables were assessed for normality and log-transformed if appropriate. Baseline comparisons were performed using chi-square tests for equal proportions or Fisher's exact tests where numbers were small and reported as n (%). Continuous normally distributed variables were compared using student t-tests or analysis of variance and reported as mean (standard deviation), while non-normally distributed data were compared using Wilcoxon rank-sum tests or Kruskal-Wallis tests and reported as median (interquartile range). Changes over time were determined using repeat measures mixed linear modelling with each patient treated as a random effect. A two-sided P value of 0.05 was considered statistically significant.

RESULTS

We screened 154 adult patients. We excluded 53 patients in accordance with pre-specified criteria (26--imminent death, 13--transfer from other ICU, eight--extracorporeal membrane oxygenation, four--severe chronic obstructive pulmonary disease, two--ICU record unavailable) and enrolled a consecutive cohort of 40 multi-trauma, 41 medical and 20 surgical patients. All patients were analysed in final analysis.

Data on Sp[O.sub.2] and Fi[O.sub.2] were collected and analysed for a total of 14,063 hours and 14,133 hours respectively. The TWA-Fi[O.sub.2] was 0.42 (95% confidence interval [CI] 0.41 to 0.44) and TWA-Sp[O.sub.2] was 97.1% (95% CI 96.8 to 97.4) for the initial seven days of MV (Table 1). During these days, patients spent most of their time above 96% Sp[O.sub.2] (Figure 1). The lower limits of the 95% CIs for 24-hour TWA-Sp[O.sub.2] on each of the first seven days of MV were >96.2% (Table 2). The ranges of 24-hour TWA-Pa[O.sub.2] and Sp[O.sub.2] for the entire study cohort were 64 to 299 mmHg and 88 to 100% respectively. The 24-hour TWA-Pa[O.sub.2] was >80 mmHg on 80% of MV days (Figure 2).

A significant variation in the achieved TWA-Sp[O.sub.2] was observed particularly when Fi[O.sub.2] requirements were >0.35 (Figure 3). TWA-Fi[O.sub.2] of [greater than or equal to] 0.35 was used to achieve TWA-Sp[O.sub.2] >95% on the majority (61%) of MV days. Of 612 MV days, a TWA-Sp[O.sub.2] of 90 to 96% was achieved on 128 (21%) days with TWA-Fi[O.sub.2] of 0.25 to 0.60; and a TWA-Sp[O.sub.2] >96% was achieved on 120 (20%) days with TWA-Fi[O.sub.2] of 0.45 to 0.95. Of 58 MV days with TWA-Fi[O.sub.2] [greater than or equal to] 0.60, a TWA-Sp[O.sub.2] [greater than or equal to] 96% occurred on 28 (48%) days. Of eight MV days with TWA-Fi[O.sub.2] >0.80, a TWA-Sp[O.sub.2] >96% occurred on three (38%) days.

There was a wide variation in clinical practice with respect to Sp[O.sub.2] achieved at comparable ALI scores (Figure 4), and particularly with Pa[O.sub.2]/Fi[O.sub.2] <200 (Figure 5). A trend to accept lower Sp[O.sub.2] with worsening ALI scores was noticed, although even on days with severe ALI scores (>2.5), the TWA-Sp[O.sub.2] varied widely from 89 to 99%. Compared to patients in the high ALI score group, those in the lower ALI score groups had higher mean Sp[O.sub.2] and Pa[O.sub.2], and spent more time at supra-normal [O.sub.2] levels (number of hours at Pa[O.sub.2] >100 mmHg, P=0.01; and number of hours at Pa[O.sub.2] >200 mmHg, P <0.0001) during the first 72 hours of MV. The Pa[O.sub.2]/ Fi[O.sub.2] on day 3 and day 6, when compared to day 0, were significantly worse in the lower ALI score group compared to the higher ALI score groups (Table 3). There were no significant differences in the average tidal volumes (P >0.5) in the three ALI subgroups during the initial three MV days, but TWA-PEEP values, as expected, were higher (P <0.0001) in the high ALI score group. Patients with lower ALI scores spent more time in higher Sp[O.sub.2] ranges compared to other subgroups (P <0.0001).

There were no differences amongst the trauma, medical and surgical patients with regard to the mean Sa[O.sub.2] (P=0.9), Pa[O.sub.2] (P=0.4), Sp[O.sub.2] (P=0.1), Fi[O.sub.2] (P=0.6), ALI score (P=0.2) or the time spent in various Sp[O.sub.2] and Fi[O.sub.2] ranges. The frequency of ABG tests was assessed in the lowest and the highest quartile of patients based on 72-hour TWA-Sa[O.sub.2] or TWA-Pa[O.sub.2]. During the initial 72 hours in the lowest quartile of patients (TWA-Sa[O.sub.2] <96%, or TWA-Pa[O.sub.2] <94 mmHg), an ABG analysis was performed every 2.8 hours compared to 3.1 hours for the highest quartile of patients (TWA-Sa[O.sub.2] > 97.4%, or TWA-Pa[O.sub.2] > 126 mmHg).

Forty-nine patients did not survive to hospital discharge. Patients who died were older, had non-trauma related admission, had higher Acute Physiology and Chronic Health Evaluation II scores and had more pre-existing comorbidities. Patients who died spent more time in lower Sp[O.sub.2] ranges although the differences were non-significant when adjusted for baseline imbalances using multivariate logistic regression. There were no significant differences in the level of Fi[O.sub.2] exposure between survivors and non-survivors.

DISCUSSION

Key findings

We conducted an observational cohort study to describe current oxygenation practice in patients who needed MV for at least 48 hours. We found that the blood oxygenation levels achieved in this cohort were 'liberal'. Patients were, on average, ventilated for several days with supra-normal Pa[O.sub.2] values. There was a wide variability in the observed mean Sp[O.sub.2] particularly when Fi[O.sub.2] requirements were more than 0.35. Large variations in the mean Sp[O.sub.2] and Pa[O.sub.2] were noticed among patients who had days with comparable ALI scores. Finally, compared to patients with higher ALI scores on day 0 of MV, patients with lower ALI scores spent more time with supra-normal Pa[O.sub.2] during the initial 72 hours of MV; and in the lower ALI score patients, mean Pa[O.sub.2]/Fi[O.sub.2] decreased significantly from day 0 to day 6 compared to patients with higher ALI score.

Relationship to previous studies

This is the first report of longitudinal measurements of the TWA oxygenation levels (Sp[O.sub.2], Fi[O.sub.2]) achieved each day during the first seven days of MV at a tertiary ICU. A study of worst blood gas within the first 24 hours of ICU admission in patients on MV, reported a mean Pa[O.sub.2] of 99 mmHg at a mean Fi[O.sub.2] of 0.50 (15). Another study examined data from the worst blood gas within the first 24 hours of ICU admission, and reported a mean Pa[O.sub.2] of 152 mmHg at a mean Fi[O.sub.2] of 0.62 in ventilated patients (16). In our study during the initial 24 hours of MV, the mean TWA-Pa[O.sub.2] of 144 mmHg and the mean TWA-Fi[O.sub.2] of 0.52 is similar to the above reports. The Fi[O.sub.2] data were also similar to those reported in other large epidemiological studies of MV (17). These results suggest that clinicians often deliver liberal amounts of [O.sub.2] in critically ill patients and obtain higher oxygenation targets, despite the absence of supportive data.

Oxygenation targets in major randomised controlled trials (RCT) including the ARDSnet study of lower tidal volumes (13) and lung open ventilation study (14) required a Sp[O.sub.2] of 88 to 95% or Pa[O.sub.2] of 55 to 80 mmHg. The mean Pa[O.sub.2] achieved in these patients with severe ALI on the first day were 76 to 88 mmHg at a mean Fi[O.sub.2] of 0.50 to 0.58. Even in these rigorous clinical trial settings, the mean levels of oxygenation achieved were either close to or exceeded the assigned upper limits. In our study, patients with high ALI scores on day 0 had mean Sp[O.sub.2], Pa[O.sub.2] and Fi[O.sub.2] levels of 96%, 111 mmHg and 0.64 respectively, all higher than recommended targets. A similar disparity between recommendations and clinical practice has been reported in other situations (18).

When Australian intensivists were asked "after how long would a stable Sp[O.sub.2] of 90% in a ventilated 50-year old-patient with ARDS cause concern?"--53% replied never, 16% said >48 hours and 11% said <one hour (19). When Canadian intensivists were asked about a patient with Sa[O.sub.2] of 85 to 90% at Fi[O.sub.2] of 0.50 to 0.60, 52% of the respondents replied that they would not change Fi[O.sub.2] (20). However, what clinicians say and what they do appear somewhat different. In our study, TWA-Sp[O.sub.2] [greater than or equal to] 96% was achieved on nearly half (48%) of the 58 MV days during which patients received TWA-Fi[O.sub.2] [greater than or equal to] 0.60. As reported, there were many ventilation days when Sp[O.sub.2] of 90 to 96% occurred despite mild-moderate levels of Fi[O.sub.2], and many days when moderate-high levels of Fi[O.sub.2] were used to achieve Sp[O.sub.2] above 96%. These observations may imply some arbitrariness in [O.sub.2] titration.

Trends in Pa[O.sub.2]/Fi[O.sub.2] have been reported to predict clinical outcomes in some conditions (21). In our study, we assessed change in Pa[O.sub.2]/Fi[O.sub.2] from day 0 to day 3 and day 6 in all three ALI subgroups. We found that Pa[O.sub.2]/Fi[O.sub.2] improved in the higher ALI score group and deteriorated in the lower ALI score group. Patients in the lower ALI score group were also exposed to liberal levels of Fi[O.sub.2] in relation to their Pa[O.sub.2] and Sa[O.sub.2] levels. This finding is consistent with a recent study that showed both exposure to higher Fi[O.sub.2] and longer duration of exposure were associated with worsening oxygenation index at 48 hours (7). It may also be a reflection of practice where clinicians use more lung-protective ventilation and take active measures to avoid fluid overload (22) in severe ALI patients. The use of lung-protective ventilation has been demonstrated in a previous RCT to induce lesser systemic and intrapulmonary inflammatory response than standard of care ventilation (23). Although the mean PEEP levels were greater in the higher ALI score group, the tidal volumes (as ml/kg predicted body weight) were similar in the three groups.

Various preclinical (24-31) and clinical (2,3,5,15-32-33-36) studies over the past few decades have shown that protracted supra-normal [O.sub.2] levels in blood and tissues may be injurious. Although the rise in arterial [O.sub.2] content is trivial when Sa[O.sub.2] is raised from 90 to 97% (37), the increase in toxic oxidants due to higher tissue [O.sub.2] levels may overwhelm anti-oxidative reserves and lead to oxidative injury, particularly in the presence of inflammation (38). On the other hand, a limited duration (<24 hours) of sub-toxic regimens of normobaric hyperoxia has been shown to exert moderate beneficial effects on the systemic and pulmonary inflammatory response in the peritonitis-induced septic shock animal models (39,40). Recently, titrated [O.sub.2] therapy (Sp[O.sub.2] 88 to 92%) during pre-hospital management was shown to reduce risk of death by 78% in chronic obstructive pulmonary disease patients (5). Contrary to the results from a previous landmark RCT (41), one RCT reported high Fi[O.sub.2] as a predictor of surgical site infection on multivariate regression analysis (32). A multicentre RCT in patients undergoing laparotomy showed that patients who received 80% [O.sub.2] compared to 30% [O.sub.2] perioperatively had a 1.5% absolute increase in 30-day mortality (P=0.13) (42) and a statistically significant increase in long-term mortality (hazard ratio 1.3, 95% CI 1.03 to 1.64, P=0.03) (33). Such data, combined with lack of quality data for other clinical situations in ICU, make it uncertain if patients on MV are optimally managed with conservative or liberal oxygenation targets.

Significance of study findings

Our study supports the view that clinicians usually target relatively high Pa[O.sub.2] and Sp[O.sub.2] values. This provides an opportunity to study whether a more conservative approach to [O.sub.2] therapy is possible and perhaps, beneficial. It also defines the characteristics of a possible control group, its mortality rates and the [O.sub.2] related parameters that could be used for such a group in RCTs. In response to these findings, we are currently designing a phase 2 multicentre trial to assess the feasibility, safety and physiological efficacy of a 'conservative' approach to [O.sub.2] therapy in mechanically ventilated patients. Given the magnitude of variability in practice and the achieved TWA-Sp[O.sub.2] of 97% (CI 96.8 to 97.4) over the initial seven days of MV, a case can be made for the 'liberal' or control arm to target a Sp[O.sub.2] of at least 96% in order to achieve a reasonable degree of separation between the mean oxygenation levels of the two groups.

Strength and limitations

The strength of this study is that we have comprehensively described the longitudinal pattern of [O.sub.2] use and the achieved oxygenation levels by investigating hourly data for the first seven days of MV at a tertiary academic centre. The 24-hour weighted averages for oxygenation-related variables in our study are described for the first time. The main limitation is that this is a single centre study. The data for initial 24 hours of MV in this study is consistent with other multicentre reports. Our sample size was sufficient to derive a point estimate for oxygenation-related variables with sufficiently narrow confidence intervals. Since we enrolled only those patients who required at least 48 hours of MV, our study may have a selection bias towards a sicker cohort of patients. Further, there could be a number of other unmeasured confounding factors that might have influenced the choice of Sp[O.sub.2] or Pa[O.sub.2] targets in the real-time clinical situation. As mixed venous or central venous blood gases were checked infrequently, we did not examine venous oxygenation or other measures of tissue oxygenation in this study. Therefore, we cannot assess whether clinicians targeted higher levels of Sp[O.sub.2] or Sa[O.sub.2] based on a lower level of venous or tissue oxygenation. However, seeking to improve tissue oxygenation by changing Sp[O.sub.2] values by a few percentage points may not be an efficient strategy.

CONCLUSIONS

The mean oxygenation levels achieved in ventilated patients were 'liberal' and quite variable, resulting in potentially higher than necessary Sp[O.sub.2], Pa[O.sub.2] and Fi[O.sub.2] values. Further research is needed to confirm validity of these findings at other centres, and clarify whether trials are possible where a more conservative approach to [O.sub.2] therapy is compared with such 'liberal' [O.sub.2] therapy.

Caption: Figure 1: Bar chart showing proportion of time spent in pre-specified Sp[O.sub.2] range.

Caption: Figure 2: Scatter plot for 24-hour weight-average Pa[O.sub.2] achieved vs ALI score on that day.

Caption: Figure 3: Scatter plot for 24-hour weight-average Sp[O.sub.2] achieved vs 24-hour weight-average Fi[O.sub.2] utilised, depicting data for 612 ventilated days. We speculate a tolerance line (bold line) that connects the lowest accepted 'Sp[O.sub.2] at Fi[O.sub.2] of 0.25' and 'Sp[O.sub.2] at Fi[O.sub.2] of 1' in the study.

Caption: Figure 4: Scatter plot for 24-hour weight-average Sp[O.sub.2] vs ALI score on that day.

Caption: Figure 5: Scatter plot for 24-hour weight-average Pa[O.sub.2]/Fi[O.sub.2] ratio.

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(38.) Motoyama T, Okamoto K, Kukita I, Hamaguchi M, Kinoshita Y, Ogawa H. Possible role of increased oxidant stress in multiple organ failure after systemic inflammatory response syndrome. Crit Care Med 2003; 31:1048-1052.

(39.) Waisman D, Brod V, Rahat MA, Amit-Cohen BC, Lahat N, Rimar D et al. Dose-related effects of hyperoxia on the lung inflammatory response in septic rats. Shock 2012; 37:95-102.

(40.) Hauser B, Barth E, Bassi G, Simon F, Groger M, Oter Set al. Hemodynamic, metabolic, and organ function effects of pure oxygen ventilation during established fecal peritonitis-induced septic shock. Crit Care Med 2009; 37:2465-2469.

(41.) Greif R, Akca O, Horn EE Kurz A, Sessler DI. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med 2000; 342:161-167.

(42.) Meyhoff CS, Wetterslev J, Jorgensen LN, Henneberg SW, Hogdall C, Lundvall Let al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA 2009; 302:1543-1550.

R. PANWAR *, G. CAPELLIER ([dagger]), N. SCHMUTZ ([double dagger]), A. DAVIES ([section]), D. J. COOPER**, M. BAILEY ([dagger][dagger]), D. BAGULEY ([double dagger][double dagger]), D. V. PILCHER ([section][section]), R. BELLOMO ***

Department of Intensive Care, The Alfred Hospital, Melbourne, Victoria, Australia

* FCICM, MD, DNB, MBBS, Staff Specialist, Department of Intensive Care, John Hunter Hospital, Newcastle, New South Wales.

([dagger]) MD, MSc, PhD, Professor, Critical Care Unit, University Hospital Besancon and University of Franche-Comte, France.

([double dagger]) MD, Registrar.

([section]) MBBS, FRACE FCICM, Associate Professor.

** FCICM, FRACE MD, MBBS, Professor, Department of Intensive Care, The Alfred Hospital; and Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University.

([dagger][dagger]) PhD, MSc (Statistics), BSc, Associate Professor, Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University.

([double dagger][double dagger]) MB, ChB, BSc, Registrar, Intensive Care Unit, Fremantle Hospital, Perth, Western Australia.

([section][section]) MRCR FRACE FCICM, Associate Professor, Department of Intensive Care, The Alfred Hospital; and Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University.

*** MBBS, MD, FRACR FCICM, Professor, Department of Intensive Care, The Austin Hospital; and Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University.

Address for correspondence: Dr R. Panwar. Email: rakshitpanwar@ hotmail.com

Accepted for publication on May 14, 2013.

Table 1
Patient characteristics and key results

                                                     Descriptive
                                                     statistics

Number of patients                                   101
Age, years, mean (SD)                                56.7 (20.5)
Females, n (%)                                       30 (30%)
Diagnosis type
  Trauma, n (%)                                      40 (40%)
  Medical, n (%)                                     41 (41%)
  Surgical, n (%)                                    20 (20%)
Admission type
  Elective, n (%)                                    6 (6%)
  Emergency, n (%)                                   95 (94%)
Admission APACHE II score, mean (SD)                 19.3 (7.6)
Day 0 SOFA score, mean (SD)                          6.5 (3.4)
Hospital length-of-stay, days, median [IQR]          20 [10.1-37.8]
Total Fi[O.sub.2] hours studied per patient, mean    143 (36.5)
 (SD)
  Hours On Fi[O.sub.2] 0.81-1.00 [median, IQR]       3 [1-5]
  Hours on Fi[O.sub.2] 0.61-0.80 [median, IQR]       2 [1-7]
  Hours on Fi[O.sub.2] 0.41-0.60 [median, IQR]       25 [10-64]
  Hours on Fi[O.sub.2] 0.21-0.40 * [median, IQR]     91 [57-132]
Total Sp[O.sub.2], hours studied per patient,        142 (36.4)
 mean (SD)
  Hours on Sp[O.sub.2] 88-91% [median, IQR]          1 [0-4]
  Hours on Sp[O.sub.2] 92-95% [median, IQR]          24 [10-52]
  Hours on Sp[O.sub.2] 96-100% [median, IQR]         108 [77-140]
7 days TWA Sp[O.sub.2], mean (CI)                    97.1 (96.8-97.4)%
7 days TWA Fi[O.sub.2], mean (CI)                    0.42 (0.41-0.44)

APACHE = Acute Physiological and Chronic Health Evaluation (10),
SD = standard deviation, SOFA = Sequential Organ Failure
Assessment (11) excluding Glasgow coma component, IQR = interquartile
range, TWA = Time weighted average, CI = confidence interval. * Hours
on Fi[O.sub.2] <0.30 (median, IQR) per patient were 0 (0-9); only 13%
of hours on Fi[O.sub.2] 0.21-0.40 were spent with Fi[O.sub.2] <0.30.

Table 2
Descriptive table of oxygenation-related variables from day 0 to day
6 of MV

                         Day 0           Day 1           Day 2

No. patients on MV       101             101             98

24-h TWA Sa[O.sub.2],    97% (1.9)       96.3 % (1.7)    96.4% (1.6)
mean (SD)

24-h TWA Sp[O.sub.2],    97.9% (1.9)     97.2 % (1.9)    97.1 % (1.9)
mean (SD)

24-h TWA Pa[O.sub.2],    144 (45)        98 (23)         93 (19)
mmHg, mean (SD)

Worst lactate, mmol/l,   2.5 [1.2-4.5]   1.7 [1.1-2.7]   1.3 [1.1-2]
median [IQR]

Mean pH, range           7.22-7.43       7.33-7.42       7.37-7.45

24-h TWA PEEP,           7.6 (2.8)       8.1 (3.1)       7.9 (3.1)
cm[H.sub.2]O, mean
(SD)

24-h TWA Fi[O.sub.2],    0.52 (0.11)     0.41 (0.11)     0.40 (0.12)
mean (SD)

Tidal volume, ml/kg      8.0 [7.3-8.8]   8.3 [7.5-8.9]   8.1 [7.5-9.5]
PBW, median [IQR]

ALI score, median        1.0 [0.3-1.7]   1.0 [0.7-2.0]   1.3 [0.3-2.0]
[IQR]

SOFA score, mean (SD)    6.5 (3.4)       6.7 (3.5)       6.1 (3.5)

                         Day 3           Day 4

No. patients on MV       90              83

24-h TWA Sa[O.sub.2],
mean (SD)

24-h TWA Sp[O.sub.2],    96.9 % (1.7)    96.6 % (2.1)
mean (SD)

24-h TWA Pa[O.sub.2],    93 (19)
mmHg, mean (SD)

Worst lactate, mmol/l,
median [IQR]

Mean pH, range

24-h TWA PEEP,           8.0 (3.1)
cm[H.sub.2]O, mean
(SD)

24-h TWA Fi[O.sub.2],    0.40 (0.11)     0.42 (0.14)
mean (SD)

Tidal volume, ml/kg
PBW, median [IQR]

ALI score, median        1.2 [0.7-2.0]
[IQR]

SOFA score, mean (SD)

                         Day 5          Day 6

No. patients on MV       72             67

24-h TWA Sa[O.sub.2],

mean (SD)

24-h TWA Sp[O.sub.2],    96.7 % (1.8)   96.6 % (1.8)
mean (SD)

24-h TWA Pa[O.sub.2],                   98 (34)
mmHg, mean (SD)

Worst lactate, mmol/l,
median [IQR]

Mean pH, range

24-h TWA PEEP,                          7.9 (2.9)
cm[H.sub.2]O, mean
(SD)

24-h TWA Fi[O.sub.2],    0.41 (0.12)    0.41 (0.12)
mean (SD)

Tidal volume, ml/kg
PBW, median [IQR]

ALI score, median                       1.0 [0.7-2.0]
[IQR]

SOFA score, mean (SD)

MV = mechanical ventilation, TWA = time-weighted average,
SD = standard deviation, IQR = interquartile range, PEEP = positive
end-expiratory pressure, PBW = predicted body weight, ALI = acute
lung injury, SOFA = Sequential Organ Failure Assessment (11)
excluding Glasgow  coma component.

Table 3
Descriptive table for patients with varying degree of ALI scores on
the day of initiation of MV

                                                      ALI score < 1

Number of patients                                    44

Day 0 ALI score, mean (SD)                            0.3 (0.04)

BMI, median [IQR]                                     25 [23.8-26.3]

Day 0 24-h TWA Pa[O.sub.2]/Fi[O.sub.2]/, median       357 [294-452]
[IQR] *

Day 0 24-h TWA PEEP, median [IQR] *                   5 [5-5.4]

Admission APACHE II score, median [IQR]               18 [13-22]

Hospital length-of-stay, days, median [IQR]           16.3 [9.3-32.8]

Day 1 worst lactate, mmol/l, median [IQR]             1.5 [1.1-2.4]
([dagger])

Day 2 worst lactate, mmol/l, median [IQR]             1.1 [1-1.7]
([dagger])

No. of ABG in first 72 h, mean (SD)                   23 (1)

Mean SOFA score for first 72 h, mean (SD) *           4.8 (0.4)

TWA-Sp[O.sub.2] for first 72 h, %, mean (SD) *        98.3 (0.2)

TWA-Pa[O.sub.2] for first 72 h, mmHg, mean (SD) *     126 (4)

TWA-Fi[O.sub.2] for first 72 h, mean (SD) *           0.39 (0.01)

Mean tidal volume for first 72 h, ml/kg PBW           8.3 (1.1)
([double dagger])

No. of h on Pa[O.sub.2] >100 mmHg in first 72 h,      32.7 (2.6)
mean (SD) ([section])

No. of h on Pa[O.sub.2] >200 mmHg in first 72 h,      6.8 [4.2-10.6]
mean (SD) *

(Day 3--Day 0) [DELTA] Pa[O.sub.2]/Fi[O.sub.2],       -82 [-153-34]
median [IQR] *

TWA-Fi[O.sub.2] for first 7 days, mean (SD) *         0.38 (0.01)

TWA-SP[O.sub.2] for first 7 days, %, mean (SD) *      97.8 (0.2)

(Day 6--Day 0) [DELTA] Pa[O.sub.2]/Fi[O.sub.2],       -86 [-152-6]
median [IQR[ ([section])

Total Sp[O.sub.2] h per patient, mean (SD)            138 (6)

  H on SP[O.sub.2] 88-91%, median [IQR] *             0 [0-1]

  H on Sp[O.sub.2] 92-95%, median [IQR] **            15 [2-35]

  H on SP[O.sub.2] 96-100%, median [IQR]              113 [92-144]

                                                      ALI score 1-2.5

Number of patients                                    41

Day 0 ALI score, mean (SD)                            1.5 (0.06)

BMI, median [IQR]                                     26.8 [23.9-30.3]

Day 0 24-h TWA Pa[O.sub.2]/Fi[O.sub.2]/, median       226 [191-281]
[IQR] *

Day 0 24-h TWA PEEP, median [IQR] *                   7.8 [6.8-9.6]

Admission APACHE II score, median [IQR]               19 [16-26]

Hospital length-of-stay, days, median [IQR]           22.2 [11.9-39]

Day 1 worst lactate, mmol/l, median [IQR]             1.7 [1.2-2.4]
([dagger])

Day 2 worst lactate, mmol/l, median [IQR]             1.3 [1.1-2]
([dagger])

No. of ABG in first 72 h, mean (SD)                   26 (1)

Mean SOFA score for first 72 h, mean (SD) *           7.5 (0.5)

TWA-Sp[O.sub.2] for first 72 h, %, mean (SD) *        97.1 (0.2)

TWA-Pa[O.sub.2] for first 72 h, mmHg, mean (SD) *     104 (3)

TWA-Fi[O.sub.2] for first 72 h, mean (SD) *           0.46 (0.02)

Mean tidal volume for first 72 h, mllkg PBW           8.6 (1.4)
([double dagger])

No. of h on Pa[O.sub.2] >100 mmHg in first 72 h,      23.5 (2.4)
mean (SD) ([section])

No. of h on Pa[O.sub.2] >200 mmHg in first 72 h,      2.9 [1.4-4.8]
mean (SD) *

(Day 3--Day 0) [DELTA] Pa[O.sub.2]/Fi[O.sub.2],       -12 [-73-38]
median [IQR] *

TWA-Fi[O.sub.2] for first 7 days, mean (SD) *         0.44 (0.01)

TWA-SP[O.sub.2] for first 7 days, %, mean (SD) *      97 (0.2)

(Day 6--Day 0) [DELTA] Pa[O.sub.2]/Fi[O.sub.2],       -23 [-56-49]
median [IQR] ([section])

Total Sp[O.sub.2] h per patient, mean (SD)            144 (6)

  H on SP[O.sub.2] 88-91%, median [IQR] *             1 [0-4]

  H on Sp[O.sub.2] 92-95%, median [IQR] **            28 [13-55]

  H on SP[O.sub.2] 96-100%, median [IQR]              108 [74-138]

                                                      ALI score >2.5

Number of patients                                    16

Day 0 ALI score, mean (SD)                            2.9 (0.08)

BMI, median [IQR]                                     25.2 [23.5-27.1]

Day 0 24-h TWA Pa[O.sub.2]/Fi[O.sub.2]/, median       175 [153-201]
[IQR] *

Day 0 24-h TWA PEEP, median [IQR] *                   10.8 [10-12.8]

Admission APACHE II score, median [IQR]               21 [15-24]

Hospital length-of-stay, days, median [IQR]           21.5 [11.2-51.2]

Day 1 worst lactate, mmol/l, median [IQR]             2.8 [1.6-4.8]
([dagger])

Day 2 worst lactate, mmol/l, median [IQR]             2.2 [1.4-2.5]
([dagger])

No. of ABG in first 72 h, mean (SD)                   25 (2)

Mean SOFA score for first 72 h, mean (SD) *           8.3 (0.8)

TWA-Sp[O.sub.2] for first 72 h, %, mean (SD) *        95.9 (0.6)

TWA-Pa[O.sub.2] for first 72 h, mmHg, mean (SD) *     96 (5)

TWA-Fi[O.sub.2] for first 72 h, mean (SD) *           0.53 (0.03)

Mean tidal volume for first 72 h, mllkg PBW           8.6 (2.3)
([double dagger])

No. of h on Pa[O.sub.2] >100 mmHg in first 72 h,      20.3 (3.3)
mean (SD) ([section])

No. of h on Pa[O.sub.2] >200 mmHg in first 72 h,      0 [0-1.8]
mean (SD) *

(Day 3--Day 0) [DELTA] Pa[O.sub.2]/Fi[O.sub.2],       17 [-15-70]
median [IQR] *

TWA-Fi[O.sub.2] for first 7 days, mean (SD) *         0.50 (0.03)

TWA-SP[O.sub.2] for first 7 days, %, mean (SD) *      95.7 (0.5)

(Day 6--Day 0) [DELTA] Pa[O.sub.2]/Fi[O.sub.2],       20 [-13-79]
median [IQR[ ([section])

Total Sp[O.sub.2] h per patient, mean (SD)            148 (9)

  H on SP[O.sub.2] 88-91%, median [IQR] *             9 [2-16]

  H on Sp[O.sub.2] 92-95%, median [IQR] **            50 [18-80]

  H on SP[O.sub.2] 96-100%, median [IQR]              90 [35-113]

Significant difference between three groups. * P <0.0001, ([dagger])
P = 0.01, ([double dagger]) P <0.05. ([section]) Predicted body
weight (as used for ARDSnet protocol): for males = 2.3 (height in
inches--60) + 50 kg; and for females = 2.3 (height in inches--60) +
45.5 kg. ALI = acute lung injury, SD = standard deviation, BMI = body
mass index, IQR = interquartile range, h = hours, TWA = time-weighted
average, APACHE = Acute Physiological and Chronic Health Evaluation,
ABG = arterial blood gas, SOFA = Sequential Organ Failure
Assessment (11) excluding Glasgow coma component, PBW = predicted
body weight.
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Article Details
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Title Annotation:Original Papers
Author:Panwar, R.; Capellier, G.; Schmutz, N.; Davies, A.; Cooper, D.J.; Bailey, M.; Baguley, D.; Pilcher,
Publication:Anaesthesia and Intensive Care
Article Type:Clinical report
Geographic Code:8AUST
Date:Jul 1, 2013
Words:7688
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