Hyperoxemia in the ICU

Article

Author: Clinical Experts Group, Hamilton Medical

Date of first publication: 20.04.2020

Hyperoxemia can be defined as an increase in arterial oxygen partial pressure (PaO2) to a level greater than 120 mmHg (16 kPa) (1, 2). It is considered to be moderate for levels ranging between 120 and 200 mmHg, and severe if PaO2 exceeds 200 mmHg (27 kPa) (3). Hyperoxemia is caused by hyperoxia (an increase in oxygen) and occurs in 22% to 50% of mechanically ventilated patients in the ICU (1, 3-6).

Takeaway messages

Hyperoxemia can be defined as an increase in arterial oxygen partial pressure (PaO2) to a level greater than 120 mmHg (16 kPa) and may occur in up to 50% of mechanically ventilated patients.
Retrospective studies have reported hyperoxemia to be associated with the duration of mechanical ventilation, the ICU stay and the hospital stay, as weil as with VAP.
Avoiding hyperoxemia and targeting physiological ranges of SpO2 and PaO2 in ICU patients may be associated with improved outcomes.
A closed-loop oxygenation controller may support this strategy in mechanically ventilated patients, and also reduce the workload for healthcare staff.

U-shaped relationship between mortality and PaO2

Retrospective studies have reported hyperoxemia to be associated with the duration of mechanical ventilation, of the ICU stay and the hospital stay, as well as with ventilator associated pneumonia (Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care. 2012;57(11):1887-1893. doi:10.4187/respcare.016967, Six S, Jaffal K, Ledoux G, Jaillette E, Wallet F, Nseir S. Hyperoxemia as a risk factor for ventilator-associated pneumonia. Crit Care. 2016;20(1):195. Published 2016 Jun 22. doi:10.1186/s13054-016-1368-48). Evidence indicates that conservative management of oxygen using pulse oximetry to target an oxygen saturation (SpO2) of between 90% and 92% is associated with decreased radiological evidence of atelectasis (Suzuki S, Eastwood GM, Goodwin MD, et al. Atelectasis and mechanical ventilation mode during conservative oxygen therapy: A before-and-after study. J Crit Care. 2015;30(6):1232-1237. doi:10.1016/j.jcrc.2015.07.0339). Severe hyperoxemia and the time spent in hyperoxemia are associated with a higher mortality rate and fewer ventilator-free days (Helmerhorst HJ, Arts DL, Schultz MJ, et al. Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care. Crit Care Med. 2017;45(2):187-195. doi:10.1097/CCM.00000000000020843). In a study focusing primarily on oxygenation during the first 24 hours of ICU admission for mechanically ventilated patients, results showed hospital mortality to have a U-shaped relationship with PaO2, whereby both the lower and higher PaO2 values were associated with higher mortality (de Jonge E, Peelen L, Keijzers PJ, et al. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Crit Care. 2008;12(6):R156. doi:10.1186/cc715010).

Comparison of conservative versus conventional oxygen therapy

In 2016, results were published from the first large, prospective randomized controlled trial to test whether a conservative protocol for oxygen supplementation to maintain PaO2 within physiological limits could improve outcomes in ICU patients (Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016;316(15):1583-1589. doi:10.1001/jama.2016.1199311). This single-center, open-label, randomized clinical trial included adult ICU patients with an expected length of stay of at least 72 hours. Exclusion criteria included pregnancy, readmission to the ICU, a decision to withhold life-sustaining treatment, immunosuppression or neutropenia, an exacerbation of COPD, and ARDS with a PaO2/FiO2 ratio below 150 mmHg. Patients were randomized into two groups, one for controlled normoxia (targeting PaO2 of 70-100 mmHg or SpO2 of 94%-98%) and one for usual care (FiO2 of 0.4 or higher as needed, targeting SpO2 of 97%-100% accepting PaO2 values of up to 150 mmHg). The primary outcome was ICU mortality, and secondary outcomes included new-onset organ failure, and bloodstream, respiratory, and surgical-site infections. The study was stopped prematurely after inclusion of 480 patients. The modified intention-to-treat population included 218 patients in the usual-care group and 216 patients in the controlled normoxia group. Sixty percent were surgical ICU patients, mostly admitted with respiratory failure (55%), and 65% of these patients were mechanically ventilated. The daily, time-weighted FiO2 and PaO2 averaged during the ICU stay were higher in the usual-care group than in the controlled normoxia group (median FiO2: 39% (35-42) versus 36% (30-40); median PaO2: 102 mmHg (88-116) versus 87 mmHg (79-97); p<0.001). ICU and hospital mortality were significantly higher in the usual-care group than in the controlled normoxia group (ICU mortality: 20% versus 12%, p=0.01; hospital mortality: 34% versus 24%, p=0.03), as was the occurrence of new shock episodes and liver failure during the ICU stay. The risk of bloodstream infections was also higher in the usual-care group than in the controlled normoxia group, and the number of hours free from mechanical ventilation was lower. There was no difference between the two groups in terms of the length of ICU and hospital stay.

Avoidance of hyperoxemia results in better outcomes

This study shows that avoidance of hyperoxemia is associated with better outcomes, and suggests that clinicians should target physiological ranges of SpO2 and PaO2 in ICU patients. In a pilot, multicenter, randomized controlled trial, a more conservative SpO2 target (88%-92%) was not associated with better outcomes when compared to a normoxia group (Panwar R, Hardie M, Bellomo R, et al. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016;193(1):43-51. doi:10.1164/rccm.201505-1019OC12).

Maintaining SpO2 within target ranges for mechanically ventilated patients requires a number of daily manual adjustments. INTELLiVENT-ASV (INTELLiVENT-ASV is not available in the US and for the HAMILTON-MR1A) offers an oxygenation controller that adjusts oxygen and PEEP according to a PEEP/FiO2 table to reach the target SpO2 set by the user. In a pilot randomized controlled trial comparing INTELLiVENT-ASV with conventional ventilation modes (volume control and pressure support) for the full duration of mechanical ventilation in 60 ICU patients, INTELLiVENT ASV was associated with signiflcantly fewer episodes of hyperoxemia, without increasing the risk of hypoxemia (A. Garnero, D. Novotni, J. Arnal. Manual versus closed loop control of oxygenation parameters during invasive ventilation: effects on hyperoxemia. Critical Care 2017, 21(Suppl 1):57. (Abstract only)13). The number of manual oxygen settings was dramatically reduced using INTELLiVENT-ASV when compared to conventional modes (median number of daily manual adjustments: 0 (0-0) versus 3 (1-8), p<0.001) (Arnal JM, Garnero A, Novotni D, et al. Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes. Minerva Anestesiol. 2018;84(1):58-67. doi:10.23736/S0375-9393.17.11963-214).

Conclusion

In conclusion, avoiding hyperoxemia and targeting physiological ranges for PaO2 and SpO2 in ICU patients is associated with improved outcomes. A closed loop oxygenation controller may help clinicians to apply this strategy in mechanically ventilated patients, and also reduce the workload for healthcare staff.

Full citations below: (de Graaff AE, Dongelmans DA, Binnekade JM, de Jonge E. Clinicians' response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2. Intensive Care Med. 2011;37(1):46-51. doi:10.1007/s00134-010-2025-z1, Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5(1):42. doi:10.1186/s13613-015-0084-62, Helmerhorst HJ, Arts DL, Schultz MJ, et al. Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care. Crit Care Med. 2017;45(2):187-195. doi:10.1097/CCM.00000000000020843, Itagaki T, Nakano Y, Okuda N, et al. Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and related factors. Respir Care. 2015;60(3):335-340. doi:10.4187/respcare.034514, Eastwood G, Bellomo R, Bailey M, et al. Arterial oxygen tension and mortality in mechanically ventilated patients. Intensive Care Med. 2012;38(1):91-98. doi:10.1007/s00134-011-2419-65, Suzuki S, Eastwood GM, Peck L, Glassford NJ, Bellomo R. Current oxygen management in mechanically ventilated patients: a prospective observational cohort study. J Crit Care. 2013;28(5):647-654. doi:10.1016/j.jcrc.2013.03.0106)

Footnotes

A. INTELLiVENT-ASV is not available in the US or on the HAMILTON-MR1

References

1. Panwar R, Hardie M, Bellomo R, et al. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016;193(1):43-51. doi:10.1164/rccm.201505-1019OC
1. de Graaff AE, Dongelmans DA, Binnekade JM, de Jonge E. Clinicians' response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2. Intensive Care Med. 2011;37(1):46-51. doi:10.1007/s00134-010-2025-z
2. Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5(1):42. doi:10.1186/s13613-015-0084-6
3. Helmerhorst HJ, Arts DL, Schultz MJ, et al. Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care. Crit Care Med. 2017;45(2):187-195. doi:10.1097/CCM.0000000000002084
4. Itagaki T, Nakano Y, Okuda N, et al. Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and related factors. Respir Care. 2015;60(3):335-340. doi:10.4187/respcare.03451
5. Eastwood G, Bellomo R, Bailey M, et al. Arterial oxygen tension and mortality in mechanically ventilated patients. Intensive Care Med. 2012;38(1):91-98. doi:10.1007/s00134-011-2419-6
6. Suzuki S, Eastwood GM, Peck L, Glassford NJ, Bellomo R. Current oxygen management in mechanically ventilated patients: a prospective observational cohort study. J Crit Care. 2013;28(5):647-654. doi:10.1016/j.jcrc.2013.03.010
7. Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care. 2012;57(11):1887-1893. doi:10.4187/respcare.01696
8. Six S, Jaffal K, Ledoux G, Jaillette E, Wallet F, Nseir S. Hyperoxemia as a risk factor for ventilator-associated pneumonia. Crit Care. 2016;20(1):195. Published 2016 Jun 22. doi:10.1186/s13054-016-1368-4
9. Suzuki S, Eastwood GM, Goodwin MD, et al. Atelectasis and mechanical ventilation mode during conservative oxygen therapy: A before-and-after study. J Crit Care. 2015;30(6):1232-1237. doi:10.1016/j.jcrc.2015.07.033
10. de Jonge E, Peelen L, Keijzers PJ, et al. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Crit Care. 2008;12(6):R156. doi:10.1186/cc7150
11. Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016;316(15):1583-1589. doi:10.1001/jama.2016.11993
13. A. Garnero, D. Novotni, J. Arnal. Manual versus closed loop control of oxygenation parameters during invasive ventilation: effects on hyperoxemia. Critical Care 2017, 21(Suppl 1):57. (Abstract only)
14. Arnal JM, Garnero A, Novotni D, et al. Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes. Minerva Anestesiol. 2018;84(1):58-67. doi:10.23736/S0375-9393.17.11963-2

Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial.

Panwar R, Hardie M, Bellomo R, et al. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016;193(1):43-51. doi:10.1164/rccm.201505-1019OC

RATIONALE

There are no randomized controlled trials comparing different oxygenation targets for intensive care unit (ICU) patients.

OBJECTIVES

To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation (IMV).

METHODS

At four multidisciplinary ICUs, 103 adult patients deemed likely to require IMV for greater than or equal to 24 hours were randomly allocated to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88-92% (n = 52) or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% (n = 51).

MEASUREMENTS AND MAIN RESULTS

The mean area under the curve and 95% confidence interval (CI) for SpO2 (93.4% [92.9-93.9%] vs. 97% [96.5-97.5%]), SaO2 (93.5% [93.1-94%] vs. 96.8% [96.3-97.3%]), PaO2 (70 [68-73] mm Hg vs. 92 [89-96] mm Hg), and FiO2 (0.26 [0.25-0.28] vs. 0.36 [0.34-0.39) in the conservative versus liberal oxygenation arm were significantly different (P < 0.0001 for all). There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality. The percentage time spent with SpO2 less than 88% in conservative versus liberal arm was 1% versus 0.3% (P = 0.03), and percentage time spent with SpO2 greater than 98% in conservative versus liberal arm was 4% versus 22% (P < 0.001). The adjusted hazard ratio for 90-day mortality in the conservative arm was 0.77 (95% CI, 0.40-1.50; P = 0.44) overall and 0.49 (95% CI, 0.20-1.17; P = 0.10) in the prespecified subgroup of patients with a baseline PaO2/FiO2 less than 300.

CONCLUSIONS

Our study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV. Larger randomized controlled trials of this intervention appear justified. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12613000505707).

Clinicians' response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2.

de Graaff AE, Dongelmans DA, Binnekade JM, de Jonge E. Clinicians' response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2. Intensive Care Med. 2011;37(1):46-51. doi:10.1007/s00134-010-2025-z

PURPOSE

Hyperoxia may induce pulmonary injury and may increase oxidative stress. In this retrospective database study we aimed to evaluate the response to hyperoxia by intensivists in a Dutch academic intensive care unit.

METHODS

All arterial blood gas (ABG) data from mechanically ventilated patients from 2005 until 2009 were extracted from an electronic storage database of a mixed 32-bed intensive care unit in a university hospital in Amsterdam. Mechanical ventilation settings at the time of the ABG tests were retrieved.

RESULTS

The results of 126,778 ABG tests from 5,498 mechanically ventilated patients were retrieved including corresponding ventilator settings. In 28,222 (22%) of the ABG tests the arterial oxygen tension (PaO(2)) was >16 kPa (120 mmHg). In only 25% of the tests with PaO(2) >16 kPa (120 mmHg) was the fraction of inspired oxygen (FiO(2)) decreased. Hyperoxia was accepted without adjustment in ventilator settings if FiO(2) was 0.4 or lower.

CONCLUSION

Hyperoxia is frequently seen but in most cases does not lead to adjustment of ventilator settings if FiO(2) <0.41. Implementation of guidelines concerning oxygen therapy should be improved and further research is needed concerning the effects of frequently encountered hyperoxia.

Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update.

Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5(1):42. doi:10.1186/s13613-015-0084-6

This review summarizes the (patho)-physiological effects of ventilation with high FiO2 (0.8-1.0), with a special focus on the most recent clinical evidence on its use for the management of circulatory shock and during medical emergencies. Hyperoxia is a cornerstone of the acute management of circulatory shock, a concept which is based on compelling experimental evidence that compensating the imbalance between O2 supply and requirements (i.e., the oxygen dept) is crucial for survival, at least after trauma. On the other hand, "oxygen toxicity" due to the increased formation of reactive oxygen species limits its use, because it may cause serious deleterious side effects, especially in conditions of ischemia/reperfusion. While these effects are particularly pronounced during long-term administration, i.e., beyond 12-24 h, several retrospective studies suggest that even hyperoxemia of shorter duration is also associated with increased mortality and morbidity. In fact, albeit the clinical evidence from prospective studies is surprisingly scarce, a recent meta-analysis suggests that hyperoxia is associated with increased mortality at least in patients after cardiac arrest, stroke, and traumatic brain injury. Most of these data, however, originate from heterogenous, observational studies with inconsistent results, and therefore, there is a need for the results from the large scale, randomized, controlled clinical trials on the use of hyperoxia, which can be anticipated within the next 2-3 years. Consequently, until then, "conservative" O2 therapy, i.e., targeting an arterial hemoglobin O2 saturation of 88-95 % as suggested by the guidelines of the ARDS Network and the Surviving Sepsis Campaign, represents the treatment of choice to avoid exposure to both hypoxemia and excess hyperoxemia.

Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care.

Helmerhorst HJ, Arts DL, Schultz MJ, et al. Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care. Crit Care Med. 2017;45(2):187-195. doi:10.1097/CCM.0000000000002084

OBJECTIVE

Emerging evidence has shown the potential risks of arterial hyperoxia, but the lack of a clinical definition and methodologic limitations hamper the interpretation and clinical relevance of previous studies. Our purpose was to evaluate previously used and newly constructed metrics of arterial hyperoxia and systematically assess their association with clinical outcomes in different subgroups in the ICU.

DESIGN

Observational cohort study.

SETTING

Three large tertiary care ICUs in the Netherlands.

PATIENTS

A total of 14,441 eligible ICU patients.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

In total, 295,079 arterial blood gas analyses, including the PaO2, between July 2011 and July 2014 were extracted from the patient data management system database. Data from all admissions with more than one PaO2 measurement were supplemented with anonymous demographic and admission and discharge data from the Dutch National Intensive Care Evaluation registry. Mild hyperoxia was defined as PaO2 between 120 and 200 mm Hg; severe hyperoxia as PaO2 greater than 200 mm Hg. Characteristics of existing and newly constructed metrics for arterial hyperoxia were examined, and the associations with hospital mortality (primary outcome), ICU mortality, and ventilator-free days and alive at day 28 were retrospectively analyzed using regression models in different subgroups of patients. Severe hyperoxia was associated with higher mortality rates and fewer ventilator-free days in comparison to both mild hyperoxia and normoxia for all metrics except for the worst PaO2. Adjusted effect estimates for conditional mortality were larger for severe hyperoxia than for mild hyperoxia. This association was found both within and beyond the first 24 hours of admission and was consistent for large subgroups. The largest point estimates were found for the exposure identified by the average PaO2, closely followed by the median PaO2, and these estimates differed substantially between subsets. Time spent in hyperoxia showed a linear and positive relationship with hospital mortality.

CONCLUSIONS

Our results suggest that we should limit the PaO2 levels of critically ill patients within a safe range, as we do with other physiologic variables. Analytical metrics of arterial hyperoxia should be judiciously considered when interpreting and comparing study results and future studies are needed to validate our findings in a randomized fashion design.

Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and related factors.

Itagaki T, Nakano Y, Okuda N, et al. Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and related factors. Respir Care. 2015;60(3):335-340. doi:10.4187/respcare.03451

BACKGROUND

Excessive supplemental oxygen causes injurious hyperoxemia. Before establishing the best P(aO2) targets for mechanically ventilated patients, it is important to understand the incidence of hyperoxemia and related factors. We investigated oxygenation in mechanically ventilated subjects in our ICU and evaluated factors related to hyperoxemia (P(aO2) > 120 mm Hg) at 48 h after initiation of mechanical ventilation.

METHODS

We retrospectively reviewed the medical records of patients admitted to our ICU from January 2010 to May 2013. Inclusion criteria were 15 y of age or older and administration of mechanical ventilation for > 48 h. Patients at risk of imminent death on admission or who had received noninvasive ventilation were excluded. We collected subject demographics, reasons for mechanical ventilation, and during mechanical ventilation, we collected arterial blood gas data and ventilator settings on the first day of intubation (T1), 48 h after initiation of mechanical ventilation (T2), and on the day of extubation (T3). Multivariable logistic regression analysis was performed to clarify independent variables related to hyperoxemia at T2.

RESULTS

For the study period, data for 328 subjects were analyzed. P(aO2) statistically significantly increased over time to 90 (interquartile range of 74-109) mm Hg at T1, 105 (89-120) mm Hg at T2, and 103 (91-119) mm Hg at T3 (P < .001), coincident with decreases in F(IO2) of 0.4 (0.3-0.5) at T1, 0.3 (0.3-0.4) at T2, and 0.3 (0.3-0.35) at T3 (P < .001). Hyperoxemia occurred in 15.6% (T1), 25.3% (T2), and 22.4% (T3) of subjects. Multivariable logistic regression analysis revealed that hyperoxemia was independently associated with age of < 40 y (odds ratio 2.6, 95% CI 1.1-6.0), Acute Physiology and Chronic Health Evaluation II scores of ≥ 30 (odds ratio 0.53, 95% CI 0.3-1.0), and decompensated heart failure (odds ratio 1.9, 95% CI 1.1 to 3.5).

CONCLUSIONS

During mechanical ventilation of critically ill subjects, P(aO2) increased, and F(IO2) decreased. One in 4 subjects were hyperoxemic at T2, and hyperoxemia persisted until T3.

Arterial oxygen tension and mortality in mechanically ventilated patients.

Eastwood G, Bellomo R, Bailey M, et al. Arterial oxygen tension and mortality in mechanically ventilated patients. Intensive Care Med. 2012;38(1):91-98. doi:10.1007/s00134-011-2419-6

PURPOSE

Early hyperoxia may be an independent risk factor for mortality in mechanically ventilated intensive care unit (ICU) patients. We examined the relationship between early arterial oxygen tension (PaO(2)) and in-hospital mortality.

METHOD

We retrospectively assessed arterial blood gases (ABG) with 'worst' alveolar-arterial (A-a) gradient during the first 24 h of ICU admission for all ventilated adult patients from 150 participating ICUs between 2000 and 2009. We used multivariate analysis in all patients and defined subgroups to determine the relationship between PaO(2) and mortality. We also studied the relationship between worst PaO(2), admission PaO(2) and peak PaO(2) in a random cohort of patients.

RESULTS

We studied 152,680 patients. Their mean PaO(2) was 20.3 kPa (SD 14.6) and mean inspired fraction of oxygen (FiO(2)) was 62% (SD 26). Worst A-a gradient ABG identified that 49.8% (76,110) had hyperoxia (PaO(2) > 16 kPa). Nineteen per cent of patients died in ICU and 26% in hospital. After adjusting for site, Simplified Acute Physiology Score II (SAPS II), age, FiO(2), surgical type, Glasgow Coma Scale (GCS) below 15 and year of ICU admission, there was an association between progressively lower PaO(2) and increasing in-hospital mortality, but not with increasing levels of hyperoxia. Similar findings were observed with a sensitivity analysis of PaO(2) derived from high FiO(2) (≥50%) versus low FiO(2) (<50%) and in defined subgroups. Worst PaO(2) showed a strong correlation with admission PaO(2) (r = 0.98) and peak PaO(2) within 24 h of admission (r = 0.86).

CONCLUSION

We found there was an association between hypoxia and increased in-hospital mortality, but not with hyperoxia in the first 24 h in ICU and mortality in ventilated patients. Our findings differ from previous studies and suggest that the impact of early hyperoxia on mortality remains uncertain.

Current oxygen management in mechanically ventilated patients: a prospective observational cohort study.

Suzuki S, Eastwood GM, Peck L, Glassford NJ, Bellomo R. Current oxygen management in mechanically ventilated patients: a prospective observational cohort study. J Crit Care. 2013;28(5):647-654. doi:10.1016/j.jcrc.2013.03.010

PURPOSE

Oxygen (O2) is the most common therapy in mechanically ventilated patients, but targets and dose are poorly understood. We aimed to describe current O2 administration and titration in such patients in an academic intensive care unit.

MATERIALS AND METHODS

In consecutive ventilated (>48 hours) patients we prospectively obtained fraction of inspired O2 (FiO2), pulse oximetry O2 saturation (SpO2) and arterial O2 tension (PaO2) every 6 hours. We calculated the amount of excess O2 delivery and the intensivists' response to hyperoxemia (SpO2>98%).

RESULTS

During 358 mechanical ventilation days in 51 critically ill patients, median calculated excess O2 delivery was 3472 L per patient. Patients spent most of their time with their SpO2>98% (59% [29-83]) and PaO2 between 80 and 120 mm Hg (59% [38-72]). In addition, 50% of all observations showed hyperoxemia and 4% severe hyperoxemia (PaO2>202.5 mm Hg). Moreover, 71% of the calculated total excess 263,841 L of O2 was delivered when the Fio2 was 0.3 to 0.5. When hyperoxemia occurred with an Fio2 between 0.3 and 0.4, for 88% of episodes, no Fio2 adjustments were made.

CONCLUSIONS

Excess O2 delivery and liberal O2 therapy were common in mechanically ventilated patients. Current O2 therapy practice may be suboptimal and further investigations are warranted.

Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury.

Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care. 2012;57(11):1887-1893. doi:10.4187/respcare.01696

BACKGROUND

Optimal titration of inspired oxygen is important to prevent hyperoxia in mechanically ventilated patients in ICUs. There is mounting evidence of the deleterious effects of hyperoxia; however, there is a paucity of data about F(IO(2)) practice and oxygen exposure among patients in ICUs. We therefore sought to assess excessive F(IO(2)) exposure in mechanically ventilated patients with acute lung injury and to evaluate the effect on pulmonary outcomes.

METHODS

From a database of ICU patients with acute lung injury identified by prospective electronic medical record screening, we identified those who underwent invasive mechanical ventilation for > 48 hours from January 1 to December 31, 2008. Ventilator settings, including F(IO(2)) and corresponding S(pO(2)), were collected from the electronic medical record at 15-min intervals for the first 48 hours. Excessive F(IO(2)) was defined as F(IO(2)) > 0.5 despite S(pO(2)) > 92%. The association between the duration of excessive exposure and pulmonary outcomes was assessed by change in oxygenation index from baseline to 48 hours and was analyzed by univariate and multivariate linear regression analysis.

RESULTS

Of 210 patients who met the inclusion criteria, 155 (74%) were exposed to excessive F(IO(2)) for a median duration of 17 hours (interquartile range 7.5-33 h). Prolonged exposure to excessive F(IO(2)) correlated with worse oxygenation index at 48 hours in a dose-response manner (P < .001.). Both exposure to higher F(IO(2)) and longer duration of exposure were associated with worsening oxygenation index at 48 hours (P < .001), more days on mechanical ventilation, longer ICU stay, and longer hospital stay (P = .004). No mortality difference was noted.

CONCLUSIONS

Excessive oxygen supplementation is common in mechanically ventilated patients with ALI and may be associated with worsening lung function.

Hyperoxemia as a risk factor for ventilator-associated pneumonia.

Six S, Jaffal K, Ledoux G, Jaillette E, Wallet F, Nseir S. Hyperoxemia as a risk factor for ventilator-associated pneumonia. Crit Care. 2016;20(1):195. Published 2016 Jun 22. doi:10.1186/s13054-016-1368-4

BACKGROUND

Consequences of hyperoxemia, such as acute lung injury, atelectasis, and reduced bacterial clearance, might promote ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between hyperoxemia and VAP.

METHODS

This retrospective observational study was performed in a 30-bed mixed ICU. All patients receiving invasive mechanical ventilation for more than 48 hours were eligible. VAP was defined using clinical, radiologic, and quantitative microbiological criteria. Hyperoxemia was defined as PaO2 > 120 mmHg. All data, except those related to hyperoxemia, were prospectively collected. Risk factors for VAP were determined using univariate and multivariate analysis.

RESULTS

VAP was diagnosed in 141 of the 503 enrolled patients (28 %). The incidence rate of VAP was 14.7 per 1000 ventilator days. Hyperoxemia at intensive care unit admission (67 % vs 53 %, OR = 1.8, 95 % CI (1.2, 29), p <0.05) and number of days spent with hyperoxemia were significantly more frequent in patients with VAP, compared with those with no VAP. Multivariate analysis identified number of days spent with hyperoxemia (OR = 1.1, 95 % CI (1.04, 1.2) per day, p = 0.004), simplified acute physiology score (SAPS) II (OR = 1.01, 95 % CI (1.002, 1.024) per point, p < 0 .05), red blood cell transfusion (OR = 1.8, 95 % CI (1.2, 2.7), p = 0.01), and proton pomp inhibitor use (OR = 1.9, 95 % CI (1.03, 1.2), p < 0.05) as independent risk factors for VAP. Other multiple regression models also identified hyperoxemia at ICU admission (OR = 1.89, 95 % CI (1.23, 2.89), p = 0.004), and percentage of days with hyperoxemia (OR = 2.2, 95 % CI (1.08, 4.48), p = 0.029) as independent risk factors for VAP.

CONCLUSION

Hyperoxemia is independently associated with VAP. Further studies are required to confirm our results.

Atelectasis and mechanical ventilation mode during conservative oxygen therapy: A before-and-after study.

Suzuki S, Eastwood GM, Goodwin MD, et al. Atelectasis and mechanical ventilation mode during conservative oxygen therapy: A before-and-after study. J Crit Care. 2015;30(6):1232-1237. doi:10.1016/j.jcrc.2015.07.033

PURPOSE

The purpose of the study is to assess the effect of a conservative oxygen therapy (COT) (target SpO2 of 90%-92%) on radiological atelectasis and mechanical ventilation modes.

MATERIALS AND METHODS

We conducted a secondary analysis of 105 intensive care unit patients from a pilot before-and-after study. The primary outcomes of this study were changes in atelectasis score (AS) of 555 chest radiographs assessed by radiologists blinded to treatment allocation and time to weaning from mandatory ventilation and first spontaneous ventilation trial (SVT).

RESULTS

There was a significant difference in overall AS between groups, and COT was associated with lower time-weighted average AS. In addition, in COT patients, change from mandatory to spontaneous ventilation or time to first SVT was shortened. After adjustment for baseline characteristics and interactions between oxygen therapy, radiological atelectasis, and mechanical ventilation management, patients in the COT group had significantly lower "best" AS (adjusted odds ratio, 0.28 [95% confidence interval {CI}, 0.12-0.66]; P=.003) and greater improvement in AS in the first 7 days (adjusted odds ratio, 0.42 [95% CI, 0.17-0.99]; P=.049). Moreover, COT was associated with significantly earlier successful weaning from a mandatory ventilation mode (adjusted hazard ratio, 2.96 [95% CI, 1.73-5.04]; P<.001) and with shorter time to first SVT (adjusted hazard ratio, 1.77 [95% CI, 1.13-2.78]; P=.013).

CONCLUSIONS

In mechanically ventilated intensive care unit patients, COT might be associated with decreased radiological evidence of atelectasis, earlier weaning from mandatory ventilation modes, and earlier first trial of spontaneous ventilation.

Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients.

de Jonge E, Peelen L, Keijzers PJ, et al. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Crit Care. 2008;12(6):R156. doi:10.1186/cc7150

INTRODUCTION

The aim of this study was to investigate whether in-hospital mortality was associated with the administered fraction of oxygen in inspired air (FiO2) and achieved arterial partial pressure of oxygen (PaO2).

METHODS

This was a retrospective, observational study on data from the first 24 h after admission from 36,307 consecutive patients admitted to 50 Dutch intensive care units (ICUs) and treated with mechanical ventilation. Oxygenation data from all admission days were analysed in a subset of 3,322 patients in 5 ICUs.

RESULTS

Mean PaO2 and FiO2 in the first 24 h after ICU admission were 13.2 kPa (standard deviation (SD) 6.5) and 50% (SD 20%) respectively. Mean PaO2 and FiO2 from all admission days were 12.4 kPa (SD 5.5) and 53% (SD 18). Focusing on oxygenation in the first 24 h of admission, in-hospital mortality was shown to be linearly related to FiO2 value and had a U-shaped relationship with PaO2 (both lower and higher PaO2 values were associated with a higher mortality), independent of each other and of Simplified Acute Physiology Score (SAPS) II, age, admission type, reduced Glasgow Coma Scale (GCS) score, and individual ICU. Focusing on the entire ICU stay, in-hospital mortality was independently associated with mean FiO2 during ICU stay and with the lower two quintiles of mean PaO2 value during ICU stay.

CONCLUSIONS

Actually achieved PaO2 values in ICU patients in The Netherlands are higher than generally recommended in the literature. High FiO2, and both low PaO2 and high PaO2 in the first 24 h after admission are independently associated with in-hospital mortality in ICU patients. Future research should study whether this association is causal or merely a reflection of differences in severity of illness insufficiently corrected for in the multivariate analysis.

Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial.

Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016;316(15):1583-1589. doi:10.1001/jama.2016.11993

Importance

Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice.

Objective

To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs).

Design, Setting, and Patients

Oxygen-ICU was a single-center, open-label, randomized clinical trial conducted from March 2010 to October 2012 that included all adults admitted with an expected length of stay of 72 hours or longer to the medical-surgical ICU of Modena University Hospital, Italy. The originally planned sample size was 660 patients, but the study was stopped early due to difficulties in enrollment after inclusion of 480 patients.

Interventions

Patients were randomly assigned to receive oxygen therapy to maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation (Spo2) between 94% and 98% (conservative group) or, according to standard ICU practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and 100% (conventional control group).

Main Outcomes and Measures

The primary outcome was ICU mortality. Secondary outcomes included occurrence of new organ failure and infection 48 hours or more after ICU admission.

Results

A total of 434 patients (median age, 64 years; 188 [43.3%] women) received conventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis. Daily time-weighted Pao2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median Pao2, 102 mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87 mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI, 0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences were lower in the conservative oxygen therapy group for new shock episode (ARR, 0.068 [95% CI, 0.020-0.120]; RR, 0.35 [95% CI, 0.16-0.75]; P = .006) or liver failure (ARR, 0.046 [95% CI, 0.008-0.088]; RR, 0.29 [95% CI, 0.10-0.82]; P = .02) and new bloodstream infection (ARR, 0.05 [95% CI, 0.00-0.09]; RR, 0.50 [95% CI, 0.25-0.998; P = .049).

Conclusions and Relevance

Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of this approach.

Trial Registration

clinicaltrials.gov Identifier: NCT01319643.

Manual versus closed loop control of oxygenation parameters during invasive ventilation: effects on hyperoxemia

A. Garnero, D. Novotni, J. Arnal. Manual versus closed loop control of oxygenation parameters during invasive ventilation: effects on hyperoxemia. Critical Care 2017, 21(Suppl 1):57. (Abstract only)

Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes.

Arnal JM, Garnero A, Novotni D, et al. Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes. Minerva Anestesiol. 2018;84(1):58-67. doi:10.23736/S0375-9393.17.11963-2

Link to article

BACKGROUND

There is an equipoise regarding closed-loop ventilation modes and the ability to reduce workload for providers. On one hand some settings are managed by the ventilator but on another hand the automatic mode introduces new settings for the user.

METHODS

This randomized controlled trial compared the number of manual ventilator setting changes between a full closed loop ventilation and oxygenation mode (INTELLiVENT-ASV®) and conventional ventilation modes (volume assist control and pressure support) in Intensive Care Unit (ICU) patients. The secondary endpoints were to compare the number of arterial blood gas analysis, the sedation dose and the user acceptance. Sixty subjects with an expected duration of mechanical ventilation of at least 48 hours were randomized to be ventilated using INTELLiVENT-ASV® or conventional modes with a protocolized weaning. All manual ventilator setting changes were recorded continuously from inclusion to successful extubation or death. Arterial blood gases were performed upon decision of the clinician in charge. User acceptance score was assessed for nurses and physicians once daily using a Likert Scale.

RESULTS

The number of manual ventilator setting changes per 24 h-period per subject was lower in INTELLiVENT-ASV® as compared to conventional ventilation group (5 [4-7] versus 10 [7-17]) manuals settings per subject per day [P<0.001]). The number of arterial blood gas analysis and the sedation doses were not significantly different between the groups. Nurses and physicians reported that INTELLiVENT-ASV® was significantly easier to use as compared to conventional ventilation (P<0.001 for nurses and P<0.01 for physicians).

CONCLUSIONS

For mechanically ventilated ICU patients, INTELLiVENT-ASV® significantly reduces the number of manual ventilator setting changes with the same number of arterial blood gas analysis and sedation dose, and is easier to use for the caregivers as compared to conventional ventilation modes.