Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry.

BACKGROUND: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence. METHODS: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO2 and PaCO2 with ABI. RESULTS: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89). CONCLUSIONS: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

Perioperative hyperoxia and myocardial injury after surgery: a randomized controlled trial.

BACKGROUND: The World Health Organization recommends hyperoxia (80% fraction of inspired oxygen, FiO2) during and for 2-6 hours following surgery to reduce surgical site infection (SSI). However, some studies suggest increased cardiovascular complications with such a high perioperative FiO2. The goal of our study was to compare the appearance of cardiovascular complications in elective adult colorectal surgery comparing the use of FiO2>0.8 versus conventional therapy (FiO2<0.4). METHODS: We performed a randomized controlled trial in intubated patients undergoing elective major colorectal surgery. Patients were randomly assigned to receive perioperative FiO2>0.8 or FiO2<0.4. The primary outcome, expressed as Odds Ratio (OR) ±95% Confidence Interval (95%CI), was the incidence of MINS (myocardial injury after noncardiac surgery evaluated for the first 4 postoperative days). Secondary outcomes included MACCE (major adverse cardiovascular and cerebral events) up to 30 postoperative days, SSI, other postoperative complications (according to Clavien-Dindo classification) and length of stay. RESULTS: We included in the final analyses 403 patients. Comparing the FiO2>0.8 and FiO2<0.4 groups, there was no difference in the appearance of MINS (6.0% vs. 10.4%; OR 0.55; 95% CI: 0.26-1.14; P=0.945). There were no differences between the groups for important secondary outcomes including MACCE to 30 days, SSI, postoperative complications or length of stay. CONCLUSIONS: Perioperative hyperoxia therapy (FiO2>0.8) with the aim of decreasing SSI did not increase cardiovascular complications after elective colorectal surgery in a general population.

Incidence of hyperoxia in trauma patients receiving pre-hospital emergency anaesthesia: results of a 5-year retrospective analysis.

BACKGROUND: Previous studies have demonstrated an association between hyperoxia and increased mortality in various patient groups. Critically unwell and injured patients are routinely given high concentration oxygen in the pre-hospital phase of care. We aim to investigate the incidence of hyperoxia in major trauma patients receiving pre-hospital emergency anesthesia (PHEA) in the pre-hospital setting and determine factors that may help guide clinicians with pre-hospital oxygen administration in these patients. METHODS: A retrospective cohort study was performed of all patients who received PHEA by a single helicopter emergency medical service (HEMS) between 1 October 2014 and 1 May 2019 and who were subsequently transferred to one major trauma centre (MTC). Patient and treatment factors were collected from the electronic patient records of the HEMS service and the MTC. Hyperoxia was defined as a PaO2 > 16 kPA on the first arterial blood gas analysis upon arrival in the MTC. RESULTS: On arrival in the MTC, the majority of the patients (90/147, 61.2%) had severe hyperoxia, whereas 30 patients (20.4%) had mild hyperoxia and 26 patients (19.7%) had normoxia. Only 1 patient (0.7%) had hypoxia. The median PaO2 on the first arterial blood gas analysis (ABGA) after HEMS handover was 36.7 [IQR 18.5-52.2] kPa, with a range of 7.0-86.0 kPa. SpO2 pulse oximetry readings before handover were independently associated with the presence of hyperoxia. An SpO2 ≥ 97% was associated with a significantly increased odds of hyperoxia (OR 3.99 [1.58-10.08]), and had a sensitivity of 86.7% [79.1-92.4], a specificity of 37.9% [20.7-57.8], a positive predictive value of 84.5% [70.2-87.9] and a negative predictive value of 42.3% [27.4-58.7] for the presence of hyperoxemia. CONCLUSION: Trauma patients who have undergone PHEA often have profound hyperoxemia upon arrival at hospital. In the pre-hospital setting, where arterial blood gas analysis is not readily available a titrated approach to oxygen therapy should be considered to reduce the incidence of potentially harmful tissue hyperoxia.

Duration of Hyperoxia and Neurologic Outcomes in Patients Undergoing Extracorporeal Membrane Oxygenation.

OBJECTIVES: To evaluate the impact of duration of hyperoxia on neurologic outcome and mortality in patients undergoing venoarterial extracorporeal membrane oxygenation. DESIGN: A retrospective analysis of venoarterial extracorporeal membrane oxygenation patients admitted to the Johns Hopkins Hospital. The primary outcome was neurologic function at discharge defined by modified Rankin Scale, with a score of 0-3 defined as a good neurologic outcome, and a score of 4-6 defined as a poor neurologic outcome. Multivariable logistic regression analysis was performed to evaluate the association between hyperoxia and neurologic outcomes. SETTING: The Johns Hopkins Hospital Cardiovascular ICU and Cardiac Critical Care Unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured first and maximum Pao2 values, area under the curve per minute over the first 24 hours, and duration of mild, moderate, and severe hyperoxia. Of 132 patients on venoarterial extracorporeal membrane oxygenation, 127 (96.5%) were exposed to mild hyperoxia in the first 24 hours. Poor neurologic outcomes were observed in 105 patients (79.6%) (102 with vs 3 without hyperoxia; p = 0.14). Patients with poor neurologic outcomes had longer exposure to mild (19.1 vs 15.2 hr; p = 0.01), moderate (14.6 vs 9.2 hr; p = 0.003), and severe hyperoxia (9.1 vs 4.0 hr; p = 0.003). In a multivariable analysis, patients with worse neurologic outcome experienced longer durations of mild (adjusted odds ratio, 1.10; 95% CI, 1.01-1.19; p = 0.02), moderate (adjusted odds ratio, 1.12; 95% CI, 1.04-1.22; p = 0.002), and severe (adjusted odds ratio, 1.19; 95% CI, 1.06-1.35; p = 0.003) hyperoxia. Additionally, duration of severe hyperoxia was independently associated with inhospital mortality (adjusted odds ratio, 1.18; 95% CI, 1.08-1.29; p < 0.001). CONCLUSIONS: In patients undergoing venoarterial extracorporeal membrane oxygenation, duration and severity of early hyperoxia were independently associated with poor neurologic outcomes at discharge and mortality.

Associationbetween hyperoxia and mortality in severely burned patients.

INTRODUCTION: The use of oxygen is a key component of acute burn resuscitation, particularly when there is concern for carbon monoxide toxicity or inhalation injury. Prior studies of critically-ill patients have shown an association between early hyperoxia and increased mortality. There are no studies to date evaluating outcomes related to excessive oxygen administration in burn patients. METHODS: We conducted a retrospective analysis of 219 severely burned patients to quantify the average amount of oxygen given during initial resuscitation, the level of carbon monoxide exposure, and to determine if early exposure to supratherapeutic oxygen was associated with increased hospital mortality or ventilator-associated pneumonia (VAP). The models were adjusted for inhalation injury and total body surface area (TBSA) burned. RESULTS: Early hyperoxia in severely burn patients is common and possibly associated with increased overall mortality, although the results were inconclusive and after adjusting for burn-specific scoring systems, we found a negative correlation between hyperoxia and mortality. Confirmed carbon monoxide poisoning was relatively uncommon, but also associated with increased mortality. Patients with elevated carboxyhemoglobin did not receive more oxygen compared to others within the cohort. CONCLUSIONS: Burn patients are exposed to higher concentrations of pure oxygen compared to other critically-ill patients, presumably for empiric treatment of carbon monoxide poisoning. Our data showed a liberal use of oxygen therapy across all patients. Considering the potentially negative effects of hyperoxia, this study exposes either a gap in clinical research or need for clearer indications.

Intra-operative hyperoxia and the risk of delirium in elderly patients after cardiac surgery.

Delirium is a common complication after cardiac surgery. The aim of our study was to determine the impact of hyperoxia episodes occurring during cardiopulmonary bypass (CBP) on the rate of delirium episodes in the postoperative period. 93 patients, aged ≥ 65, who underwent elective cardiac surgery (CBP <90 minutes) were enrolled. The occurrence of delirium episodes was examined every 12 hours for three days after surgery. Eleven patients (11.8%) developed postoperative delirium (POD (+)) and 83 did not (POD (-)). More incidences of severe hyperoxia (PaO2 ≥ 26.6kPa) during CBP were observed in the POD (+) group: 64% had ≥ 2 episodes of hyperoxia, 27% ≥ 3, and 18% ≥ 4, while in the POD (-) group: 42%, 13% and 1%, respectively (P=0.02). Patients in the POD (+) group had a higher maximum PaO2 during CBP than the POD (-) group (37 ± 5.8 vs 31.6 ± 6.6 kPa; P=0.01) and a higher mean PaO2 (30.1 ± 4.5 vs 26.1 ± 5.6 kPa; P=0.01). The optimal maximum PaO2 cut-off point for the occurrence of delirium was 33.2 kPa (AUC 0.72, P=0.001, sensitivity 75%, specificity 38%). We conclude that CBP hyperoxia episodes may be a risk factor associated with the occurrence of postoperative delirium.

Oxygen metabolism and oxygenation of the newborn.

The premature infant is to some extent protected from hypoxia, however defense against hyperoxia is poorly developed. The optimal assessment of oxygenation is to measure oxygen delivery and extraction. At the bedside PaO2 and SpO2 are approximations of oxygenation at the tissue level. After birth asphyxia it is crucial to know whether or not to give oxygen supplementation, when, how much, and for how long. Oxygen saturation targets in the delivery room have been studied, but the optimal targets might still be unknown because factors like gender and delayed cord clamping influence saturation levels. However, SpO2 > 80% at 5 min of age is associated with favorable long term outcome in preterm babies. Immature infants most often need oxygen supplementation beyond the delivery room. Predefined saturation levels, and narrow alarm limits together with the total oxygen exposure may impact on development of oxygen related diseases like ROP and BPD. Hyperoxia is a strong trigger for genetic and epigenetic changes, contributing to the development of these conditions and perhaps lifelong changes.

Supplemental Intraoperative Oxygen Does Not Promote Acute Kidney Injury or Cardiovascular Complications After Noncardiac Surgery: Subanalysis of an Alternating Intervention Trial.

BACKGROUND: Perioperative hyperoxia has been recommended by the World Health Organization and the Centers for Disease Control and Prevention for the prevention of surgical site infections. Based on animal studies and physiological concerns, the kidneys and heart may be at risk from hyperoxia. We therefore conducted 2 unplanned subanalyses of a previous alternating cohort trial in which patients having colorectal surgery were assigned to either 30% or 80% inspired intraoperative oxygen. Specifically, we tested 2 coprimary hypotheses: (1) hyperoxia increases the incidence of acute kidney injury (AKI) within 7 postoperative days (PODs); and (2) hyperoxia worsens a composite of myocardial injury, in-hospital cardiac arrest, and 30-day mortality. METHODS: The underlying controlled trial included 5749 colorectal surgeries in 4481 patients, with the exposure alternating between 30% and 80% fraction of inspired oxygen (FIO2) during general anesthesia at 2-week intervals over a period of 39 months. AKI was defined as a 1.5-fold increase in creatinine from the preoperative level to the highest value measured during the initial 7 PODs. Myocardial injury was defined by fourth-generation troponin-T level >0.03 ng/mL. We assessed the effect of 80% vs 30% oxygen on the outcomes using generalized estimating equation (GEE) logistic models that adjusted for the possible within-patient correlation across multiple potential operations for a patient on different visits. RESULTS: For the AKI outcome, 2522 surgeries were allocated to 80% oxygen and 2552 to 30% oxygen. Hyperoxia had no effect on the primary outcome of postoperative AKI, with an incidence of 7.7% in the 80% oxygen group and 7.7% in the 30% oxygen group (relative risk = 0.99; 95% confidence interval [CI], 0.82-1.2; P = .95). One thousand six hundred forty-seven surgeries (all with scheduled troponin monitoring) were analyzed for the composite cardiovascular outcome. Hyperoxia had no effect on the collapsed composite of myocardial injury, cardiac arrest, and 30-day mortality, nor on any of its components (estimated relative risk = 0.71; 95% CI, 0.44-1.16; P = .17). CONCLUSIONS: We found no evidence that intraoperative hyperoxia causes AKI or cardiovascular complications in adults undergoing colorectal surgery. Consequently, we suggest that clinicians select intraoperative inspired oxygen fraction based on other considerations.

The Search for Optimal Oxygen Saturation Targets in Critically Ill Patients: Observational Data From Large ICU Databases.

BACKGROUND: Although low oxygen saturations are generally regarded as deleterious, recent studies in ICU patients have shown that a liberal oxygen strategy increases mortality. However, the optimal oxygen saturation target remains unclear. The goal of this study was to determine the optimal range by using real-world data. METHODS: Replicate retrospective analyses were conducted of two electronic medical record databases: the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care III database (MIMIC). Only patients with at least 48 h of oxygen therapy were included. Nonlinear regression was used to analyze the association between median pulse oximetry-derived oxygen saturation (Spo2) and hospital mortality. We derived an optimal range of Spo2 and analyzed the association between the percentage of time within the optimal range of Spo2 and hospital mortality. All models adjusted for age, BMI, sex, and Sequential Organ Failure Assessment score. Subgroup analyses included ICU types, main diagnosis, and comorbidities. RESULTS: The analysis identified 26,723 patients from eICU-CRD and 8,564 patients from MIMIC. The optimal range of Spo2 was 94% to 98% in both databases. The percentage of time patients were within the optimal range of Spo2 was associated with decreased hospital mortality (OR of 80% vs 40% of the measurements within the optimal range, 0.42 [95% CI, 0.40-0.43] for eICU-CRD and 0.53 [95% CI, 0.50-0.55] for MIMIC). This association was consistent across subgroup analyses. CONCLUSIONS: The optimal range of Spo2 was 94% to 98% and should inform future trials of oxygen therapy.

Association of Severe Hyperoxemia Events and Mortality Among Patients Admitted to a Pediatric Intensive Care Unit.

Importance: A high Pao2, termed hyperoxemia, is postulated to have deleterious health outcomes. To date, the association between hyperoxemia during the ongoing management of critical illness and mortality has been incompletely evaluated in children. Objective: To examine whether severe hyperoxemia events are associated with mortality among patients admitted to a pediatric intensive care unit (PICU). Design, Setting, and Participants: A retrospective cohort study was conducted over a 10-year period (January 1, 2009, to December 31, 2018); all 23 719 PICU encounters at a quaternary children's hospital with a documented arterial blood gas measurement were evaluated. Exposures: Severe hyperoxemia, defined as Pao2 level greater than or equal to 300 mm Hg (40 kPa). Main Outcomes and Measures: The highest Pao2 values during hospitalization were dichotomized according to the definition of severe hyperoxemia and assessed for association with in-hospital mortality using logistic regression models incorporating a calibrated measure of multiple organ dysfunction, extracorporeal life support, and the total number of arterial blood gas measurements obtained during an encounter. Results: Of 23 719 PICU encounters during the inclusion period, 6250 patients (13 422 [56.6%] boys; mean [SD] age, 7.5 [6.6] years) had at least 1 measured Pao2 value. Severe hyperoxemia was independently associated with in-hospital mortality (adjusted odds ratio [aOR], 1.78; 95% CI, 1.36-2.33; P < .001). Increasing odds of in-hospital mortality were observed with 1 (aOR, 1.47; 95% CI, 1.05-2.08; P = .03), 2 (aOR, 2.01; 95% CI, 1.27-3.18; P = .002), and 3 or more (aOR, 2.53; 95% CI, 1.62-3.94; P < .001) severely hyperoxemic Pao2 values obtained greater than or equal to 3 hours apart from one another compared with encounters without hyperoxemia. A sensitivity analysis examining the hypothetical outcomes of residual confounding indicated that an unmeasured binary confounder with an aOR of 2 would have to be present in 37% of the encounters with severe hyperoxemia and 0% of the remaining cohort to fail to reject the null hypothesis (aOR of severe hyperoxemia, 1.31; 95% CI, 0.99-1.72). Conclusions and Relevance: Greater numbers of severe hyperoxemia events appeared to be associated with increased mortality in this large, diverse cohort of critically ill children, supporting a possible exposure-response association between severe hyperoxemia and outcome in this population. Although further prospective evaluation appears to be warranted, this study's findings suggest that guidelines for ongoing management of critically ill children should take into consideration the possible detrimental effects of severe hyperoxemia.

Incidence of Hyperoxia in Combat Wounded in Iraq and Afghanistan: A Potential Opportunity for Oxygen Conservation.

INTRODUCTION: Oxygen supplementation is frequently used in critically injured trauma casualties in the combat setting. Oxygen supplies in the deployed setting are limited so excessive use of oxygen may unnecessarily consume this limited resource. We describe the incidence of supraphysiologic oxygenation (hyperoxia) within casualties in the Department of Defense Trauma Registry (DoDTR). METHODS: This is a subanalysis of previously published data from the DoDTR - we isolated casualties with a documented arterial blood gas (ABG) and categorized hyperoxia as an arterial oxygen >100 mmHg and extreme hyperoxia > 300 mmHg (a subset of hyperoxia). We defined serious injuries as those with an Abbreviated Injury Score (AIS) of 3 or greater. We defined a probable moderate traumatic brain injury of those with an AIS of 3 or greater for the head region and at least one Glasgow Coma Scale at 8 or less. RESULTS: Our initial search yielded 28,222 casualties, of which 10,969 had at least one ABG available. Within the 10,969, the proportion of casualties experiencing hyperoxia in this population was 20.6% (2,269) with a subset of 4.1% (452) meeting criteria for extreme hyperoxia. Among those with hyperoxia, the median age was 25 years (IQR 21-30), most were male (96.8%), most frequently US forces (41.4%), injured in Afghanistan (68.3%), injured by explosive (61.1%), with moderate injury scores (median 17, IQR 10-26), and most (93.8%) survived to hospital discharge. A total of 17.8% (1,954) of the casualties underwent endotracheal intubation: 27.5% (538 of 1,954) prior to emergency department (ED) arrival and 72.5% (1,416 of 1,954) within the ED. Among those intubated in the prehospital setting, upon ED arrival 35.1% (189) were hyperoxic, and a subset of 5.6% (30) that were extremely hyperoxic. Among those intubated in the ED, 35.4% (502) were hyperoxic, 7.9% (112) were extremely hyperoxic. Within the 1,277 with a probable TBI, 44.2% (565) experienced hyperoxia and 9.5% (122) met criteria for extreme hyperoxia. CONCLUSIONS: In our dataset, more than 1 in 5 casualties overall had documented hyperoxia on ABG measurement, 1 in 3 intubated casualties, and almost 1 in 2 TBI casualties. With limited oxygen supplies in theater and logistical challenges with oxygen resupply, efforts to avoid unnecessary oxygen supplementation may have material impact on preserving this scarce resource and avoid potential detrimental clinical effects from supraphysiologic oxygen concentrations.

Early hyperoxemia is not associated with cardiac arrest outcome.

AIM: Studies suggest that hyperoxemia increases short-term mortality after cardiopulmonary resuscitation (CPR), but the effect of hyperoxemia on long-term outcomes is unclear. We determined the prevalence of early hyperoxemia after CPR and its association with long-term neurological outcome and mortality. METHODS: We analysed data from adult cardiac arrest patients treated after CPR in tertiary ICUs during 2005-2013. We retrieved data from the resuscitation and the first arterial blood sample collected after return of spontaneous circulation (ROSC) (severe hyperoxemia defined as PaO2 > 40 kPa and moderate as PaO2 16-40 kPa). We inspected two outcomes, neurological performance at one year after resuscitation according to the Cerebral Performance Category and one-year mortality. We used logistic regression to test associations between hyperoxemia and the outcome and interaction analyses to test the effect of hyperoxemia exposure on the outcomes in smaller subgroups. RESULTS: Of 1110 patients 11% had severe hyperoxemia, prevalence was 10% for out-of-hospital arrests, 13% for in-hospital arrests and 9% for in-ICU arrests. In total 585(53%) patients had an unfavourable neurological outcome. Compared to normoxemia, severe (Odds ratio [OR] 0.81, 95% confidence interval [CI] 0.50-1.30) and moderate hyperoxemia (OR 0.94 95%CI 0.69-1.27) did not associate with neurological outcome. Additionally, hyperoxemia had no association with mortality. In subgroup analyses there were no significant associations between severe hyperoxemia and outcomes regardless of cardiac arrest location, initial rhythm or time-to-ROSC. CONCLUSION: We found no association between early post-arrest hyperoxemia and unfavourable outcome. Subgroup analysis found no differential effect depending on arrest location, initial rhythm or time-to-ROSC.

Adherence to oxygen saturation targets increased in preterm infants when a higher target range and tighter alarm limits were introduced.

AIM: European consensus guidelines published in May 2013 recommended a target peripheral capillary oxygen saturation (SpO2 ) range of 90-95% for preterm infants. These were incorporated into guidelines at the Karolinska University Hospital, Sweden, in November 2013. This study compared clinical practice before and after those local guidelines. METHODS: We included infants who were born between 23 + 0 and 30 + 6 weeks from January 1, 2013 to December, 31 2015 and received intensive care in two Karolinska units. The lower saturation target of 88-92% and alarm limits of 85-95% used before November 2013 were compared to the new higher saturation target of 90-95% and alarm limits of 89-96%. RESULTS: Data from 399 infants were analysed. The mean SpO2 was 92.4% with the higher target (n = 301) and 91.1% with the lower target (n = 98). Using the higher instead of lower target meant that the SpO2 was within the prescribed target range more frequently (51% versus 30%) and the proportion of time with SpO2 >95% was increased by 9% (95% confidence interval 7-11%, p < 0.001). CONCLUSION: The higher saturation target and tighter alarm limits led to higher mean oxygen saturation, increased adherence to the target and increased time with hyperoxaemia.

The effect of hyperoxia on mortality in critically ill patients: a systematic review and meta analysis.

BACKGROUND: Studies investigating the role of hyperoxia in critically ill patients have reported conflicting results. We did this analysis to reveal the effect of hyperoxia in the patients admitted to the intensive care unit (ICU). METHODS: Electronic databases were searched for all the studies exploring the role of hyperoxia in adult patients admitted to ICU. The primary outcome was mortality. Random-effect model was used for quantitative synthesis of the adjusted odds ratio (aOR). RESULTS: We identified 24 trials in our final analysis. Statistical heterogeneity was found between hyperoxia and normoxia groups in patients with mechanical ventilation (I2 = 92%, P < 0.01), cardiac arrest(I2 = 63%, P = 0.01), traumatic brain injury (I2 = 85%, P < 0.01) and post cardiac surgery (I2 = 80%, P = 0.03). Compared with normoxia, hyperoxia was associated with higher mortality in overall patients (OR 1.22, 95% CI 1.12~1.33), as well as in the subgroups of cardiac arrest (OR 1.30, 95% CI 1.08~1.57) and extracorporeal life support (ELS) (OR 1.44, 95% CI 1.03~2.02). CONCLUSIONS: Hyperoxia would lead to higher mortality in critically ill patients especially in the patients with cardiac arrest and ELS.

Hyperoxia and Hypocapnia During Pediatric Extracorporeal Membrane Oxygenation: Associations With Complications, Mortality, and Functional Status Among Survivors.

OBJECTIVES: To determine the frequency of hyperoxia and hypocapnia during pediatric extracorporeal membrane oxygenation and their relationships to complications, mortality, and functional status among survivors. DESIGN: Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network. SETTING: Eight Collaborative Pediatric Critical Care Research Network-affiliated hospitals. PATIENTS: Age less than 19 years and treated with extracorporeal membrane oxygenation. INTERVENTIONS: Hyperoxia was defined as highest PaO2 greater than 200 Torr (27 kPa) and hypocapnia as lowest PaCO2 less than 30 Torr (3.9 kPa) during the first 48 hours of extracorporeal membrane oxygenation. Functional status at hospital discharge was evaluated among survivors using the Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: Of 484 patients, 420 (86.7%) had venoarterial extracorporeal membrane oxygenation and 64 (13.2%) venovenous; 69 (14.2%) had extracorporeal membrane oxygenation initiated during cardiopulmonary resuscitation. Hyperoxia occurred in 331 (68.4%) and hypocapnia in 98 (20.2%). Hyperoxic patients had higher mortality than patients without hyperoxia (167 [50.5%] vs 48 [31.4%]; p < 0.001), but no difference in functional status among survivors. Hypocapnic patients were more likely to have a neurologic event (49 [50.0%] vs 143 (37.0%]; p = 0.021) or hepatic dysfunction (49 [50.0%] vs 121 [31.3%]; p < 0.001) than patients without hypocapnia, but no difference in mortality or functional status among survivors. On multivariable analysis, factors independently associated with increased mortality included highest PaO2 and highest blood lactate concentration in the first 48 hours of extracorporeal membrane oxygenation, congenital diaphragmatic hernia, and being a preterm neonate. Factors independently associated with lower mortality included meconium aspiration syndrome. CONCLUSIONS: Hyperoxia is common during pediatric extracorporeal membrane oxygenation and associated with mortality. Hypocapnia appears to occur less often and although associated with complications, an association with mortality was not observed.

Incidence of hyperoxia and related in-hospital mortality in critically ill patients: a retrospective data analysis.

BACKGROUND: Mechanical ventilation with oxygen is life-saving, however, may result in hyperoxia. The aim was to analyse the incidence and duration of hyperoxia burden and related in-hospital mortality in critically ill patients. METHODS: Patients of all ages admitted to intensive care units (ICUs) and with mechanical ventilation for at least seven consecutive days were included in this single centre retrospective medical record audit. The main outcome measure was time-weighted arterial partial pressure of oxygen (PaO2 ) over 7 days. Logistic regression for association with in-hospital mortality and propensity score matching was performed. RESULTS: In total, 20,889 arterial blood gases of 419 patients were analysed. Time-weighted mean PaO2 was 14.0 ± 2.4 kPa. Time-weighted mean FiO2 was 49.2 ± 12.1%. Seventy-six (18.1%) patients showed continuous hyperoxia exposure, defined as time-weighted mean PaO2 > 16 kPa. Duration of hyperoxia, hypoxia (PaO2 < 8 kPa) and normoxia (PaO2 8-16 kPa) were 37.9 ± 31.0 h (23.7%), 4.9 ± 9.5 h (3.1%), and 116.8 ± 29.6 h (73.2%). Hyperoxia occurred especially at low to moderate FiO2 in patients of first and second age quartiles (1-57 years) with smaller SAPS2 score. In-hospital mortality of patients with hyperoxia (32.9%) or normoxia did not differ (35.9%; P = 0.691). Conditional logistic regression showed no association between hyperoxia and in-hospital mortality (OR 1.46; 95%CI 0.72-2.96; P = 0.29). CONCLUSION: Substantial hyperoxia burden was observed in ICU patients. Young patients with less comorbidities showed hyperoxic episodes more often, especially with lower FiO2 . Hyperoxia during 7 days of mechanical ventilation did not correlate to increased in-hospital mortality.

The Cumulative Partial Pressure of Arterial Oxygen Is Associated With Neurological Outcomes After Cardiac Arrest Treated With Targeted Temperature Management.

OBJECTIVE: Hyperoxia could lead to a worse outcome after cardiac arrest. The aim of this study was to investigate the relationship between the cumulative partial pressure of arterial oxygen (PaO2) and neurological outcomes after cardiac arrest treated with targeted temperature management. DESIGN: Retrospective analysis of a prospective cohort. SETTING: An academic tertiary care hospital. PATIENTS: A total of 187 consecutive patients treated with targeted temperature management after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the curve of PaO2 for different cutoff values of hyperoxia (≥ 100, ≥ 150, ≥ 200, ≥ 250, and ≥ 300 mm Hg) with different time intervals (0-24, 0-6, and 6-24 hr after return of spontaneous circulation) was calculated for each patient using the trapezoidal method. The primary outcome was the neurologic outcome, as defined by the cerebral performance category, at 6 months after cardiac arrest. Of 187 subjects, 77 (41%) had a good neurologic outcome at 6 months after cardiac arrest. The median age was 54 (43-69) years, and 128 (68%) were male. The area under the curve of PaO2 with cutoff values of greater than or equal to 200, greater than or equal to 250, and greater than or equal to 300 was higher in the poor outcome group at 0-6 and 0-24 hours. The adjusted odds ratios of area under the curve of PaO2 greater than or equal to 200 mm Hg were 1.659 (95% CI, 1.194-2.305) for 0-24 hours after return of spontaneous circulation and 1.548 (95% CI, 1.086-2.208) for 0-6 hours after return of spontaneous circulation. With a higher cumulative exposure to oxygen tension, we found significant increasing trends in the adjusted odds ratio for poor neurologic outcomes. CONCLUSION: In a new method for PaO2 analysis, cumulative exposure to hyperoxia was associated with neurologic outcomes in a dose-dependent manner. Greater attention to oxygen supply during the first 6 hours appears to be important for outcome after cardiac arrest.

Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of primarily premature infants that results from an imbalance between lung injury and repair in the developing lung. BPD is the most common respiratory morbidity in preterm infants, which affects nearly 10, 000 neonates each year in the United States. Over the last two decades, the incidence of BPD has largely been unchanged; however, the pathophysiology has changed with the substantial improvement in the respiratory management of extremely low birth weight (ELBW) infants. Here we have attempted to comprehensively review and summarize the current literature on the pathogenesis and pathophysiology of BPD. Our goal is to provide insight to help further progress in preventing and managing severe BPD in the ELBW infants.

Automatic versus manual oxygen administration in the emergency department.

Oxygen is commonly administered in hospitals, with poor adherence to treatment recommendations.We conducted a multicentre randomised controlled study in patients admitted to the emergency department requiring O2 ≥3 L·min-1 Patients were randomised to automated closed-loop or manual O2 titration during 3 h. Patients were stratified according to arterial carbon dioxide tension (PaCO2 ) (hypoxaemic PaCO2 ≤45 mmHg; or hypercapnic PaCO2 >45-≤55 mmHg) and study centre. Arterial oxygen saturation measured by pulse oximetry (SpO2 ) goals were 92-96% for hypoxaemic, or 88-92% for hypercapnic patients. Primary outcome was % time within SpO2 target. Secondary endpoints were hypoxaemia and hyperoxia prevalence, O2 weaning, O2 duration and hospital length of stay.187 patients were randomised (93 automated, 94 manual) and baseline characteristics were similar between the groups. Time within the SpO2 target was higher under automated titration (81±21% versus 51±30%, p<0.001). Time with hypoxaemia (3±9% versus 5±12%, p=0.04) and hyperoxia under O2 (4±9% versus 22±30%, p<0.001) were lower with automated titration. O2 could be weaned at the end of the study in 14.1% versus 4.3% patients in the automated and manual titration group, respectively (p<0.001). O2 duration during the hospital stay was significantly reduced (5.6±5.4 versus 7.1±6.3 days, p=0.002).Automated O2 titration in the emergency department improved oxygenation parameters and adherence to guidelines, with potential clinical benefits.