Central venous oxygen saturation (ScvO₂), a complex physiologic parameter, is being widely used as a resuscitation goal in critically ill patients 123, although several limitations may preclude a clear interpretation of its changes 4. Early therapeutic interventions applied rather simultaneously after hospital or intensive care unit (ICU) admission, may affect the oxygen transport (DO₂)/oxygen consumption (VO₂) balance and ScvO₂ in an unpredictable direction. The uncommon finding of low ScvO₂ values in critically ill ICU patients may be explained by the predominately positive impact of these early interventions 56.

More than 70% of critically ill patients undergo emergency intubation during ICU stay 678, a maneuver with strong and eventually divergent effects on the physiologic determinants of DO₂ and VO₂. The final impact of emergency intubation on ScvO₂ may be unpredictable since it could potentially increase ScvO₂ by blunting regional VO₂, or eventually decrease it, particularly in hemodynamically unstable or hypovolemic patients, due to the negative effects of sedation and positive intra-thoracic pressure on cardiac output. Of note, 53% of septic patients were intubated during the study period in the early-goal directed therapy (EGDT) trial 1, but the impact of this intervention on ScvO₂ was not reported, nor has it been studied thereafter.

Our aim was to study the specific impact of this isolated maneuver on ScvO₂ in critically ill septic and non-septic patients subjected to emergency intubation.

This prospective observational multicenter study was performed in three university-affiliated hospitals between December 2006 and March 2008. The study was approved by the corresponding institutional review boards. Surrogates signed an informed consent for ICU treatment including the intubation procedure.

A total of 108 critically ill patients requiring emergency intubation were included in this study. Forty-two patients (40.8%) were intubated for respiratory failure, 17 (16.5%) for circulatory failure, and the remaining 44 (42.7%) for mixed causes. Five patients were excluded from analysis because measurements could not be obtained in due time: two with difficult intubation and three for severe cardiovascular instability during the procedure. In these patients, samples were taken only after 35 to 50 minutes, and ScvO₂ ranged from 59 to 65% with no improvement compared with pre-intubation values.

Baseline characteristics of the remaining 103 patients are shown in Table 1. Forty-eight patients (46.6%) had severe sepsis (more frequently respiratory (43%) and abdominal (40%) sources). These patients had septic shock, community-acquired pneumonia, pancreatitis, and postoperative sepsis, with different organ dysfunction profiles including acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) in 20 (42%). Fifty (91%) of the non-septic patients were of cardiogenic origin (including acute circulatory failure, acute coronary syndromes, pulmonary edema, pulmonary thromboembolism, life-threatening arrhythmias, and congestive heart failure).

At intubation, 41 patients were macro-hemodynamically stable without vasoactive drugs, and the others used either vasopressors or inotropes as shown in Table 1. Basal arterial lactate was 2.27 ± 1.77 mmol/L. Severe septic patients had been previously resuscitated according to Surviving Sepsis Campaign guidelines 2 including fluid challenge in all and vasopressors in 25 patients, mostly norepinephrine (Table 1). Source control was ongoing in all. In the cardiogenic patients, 24 were receiving inotropic support with dobutamine, milrinone, or levosimendan (Table 1). Only nine patients were under vasodilator therapy. Hospital mortality for the whole group was 22%.

No severe adverse events such as arrhythmias or cardiac arrest during intubation were registered. Thirty-three patients used vasopressors before intubation (Table 1), of whom 14 required a transitory increase in norepinephrine dose. Of the reminder 70 patients, 17 required one or two 8 mg ephedrine bolus plus an additional 250 ml normal saline bolus during the study protocol.

In the whole group, ScvO₂ increased after intubation in 84 of 103 patients (81.6%) from 61.8 ± 12.6% to 68.9 ± 12.2% (P < 0.0001; Table 2 and Figure 1). ScvO₂ increased also significantly in both septic and non-septic patients (Table 2). Changes in ScvO₂ were independent from changes in SaO₂ as demonstrated by a non-significant correlation between both (r² = 0.014, P = 0.242; Figure 2). As a whole, 78 (75.7%) patients were intubated with a ScvO₂ less than 70% and 21 (26.9%) normalized the parameter after this sole intervention.

We also explored the impact of the maneuver over ScvO₂ according to pre-intubation values of ScvO₂ and SaO₂. We found a significant increase in ScvO₂ in patients with baseline ScvO₂ less than 70% independent of baseline SaO_2. Only patients with ScvO₂ more than 70% failed to increase the parameter after intubation (Table 3).

As a whole, oxygen extraction decreased in 56 patients (54.4%) by more than 2.5%, but increased more than 2.5% in 32 patients (31%) compared with baseline. As expected, patients who decreased O₂ER after intubation, exhibited higher pre-intubation respiratory rates (30.7 ± 6.3 vs. 25.3 ± 4.0; P = 0.047). Mean arterial pressure (MAP), HR, and RR decreased also significantly after intubation (Table 2).

Septic and non-septic subgroups showed the same trends in physiologic variables after intubation, except for a higher decrease in O₂ER in septic patients, and in MAP in the non-septic subgroup.

Our study demonstrates that emergency intubation markedly improves ScvO₂ in both septic and non-septic patients. Changes in ScvO₂ were consistent across the studied subgroups, regardless of the cause of intubation and baseline arterial oxygen saturation. In contrast, the effects on oxygen extraction were more variable. In almost 30% of the patients this sole maneuver increased ScvO₂ over 70%, a level considered as a resuscitation goal by current guidelines 2.

The role of ScvO₂ as a reliable marker of global dysoxia has been widely accepted 12. Nevertheless, no study has replicated the very low ScvO₂ values of the EGDT trial 1. Low ScvO₂ values are present in less than 21% of ICU patients with septic shock or respiratory failure 56. Interestingly, the study by van Beest and colleagues 83% of patients were already intubated before the first ScvO₂ sampling 6. In fact, our low pre-intubation ScvO₂ values in septic patients closely resemble baseline data from the EGDT trial 1, although ScvO₂ values after intubation are quite similar to those previously reported in the ICU setting 569.

Is normalization of ScvO₂ after intubation a reliable indicator of a successful resuscitation? Our data show that ScvO₂, as expected, is highly sensitive to intubation. We believe that early normalization of this sole parameter after intubation should be interpreted with caution. Either an increase in SaO₂ in some patients, or a decrease in cerebral and respiratory muscles VO₂, may both increase ScvO₂, but not necessarily reflect an improvement in global perfusion. In concordance, a recent study challenged the sensitivity of a ScvO₂ more than 70% as a marker of an adequate DO₂/VO₂ balance after resuscitation in the ICU setting 10. Therefore, we strongly believe that a multimodal approach including other parameters such as clinical perfusion, venous-arterial partial pressure of carbon dioxide gradient or lactate, must be used to assess perfusion, particularly after intubation.

Although the aim of our clinical observational study was to evaluate the specific impact of emergency intubation on ScvO₂ and not to explore the determinants of this response, some physiologic considerations are important. Several studies have shown that sedation and connection to mechanical ventilation can decrease oxygen consumption in the brain and respiratory muscles, the principal determinants of VO₂ in the territories drained by the superior vena cava 11121314151617. Supporting this concept, and as expected, we found that patients with higher pre-intubation RR exhibited more pronounced decreases in O₂ER after the maneuver. Conversely, DO₂ can also be affected by emergency intubation and mechanical ventilation either by increases in SaO₂ or changes in cardiac output. The increase in intra-thoracic pressure and decrease in sympathetic outflow induced by the maneuver favor a decrease in venous return, vasomotor tone, and cardiac output. Thus, sometimes divergent changes in DO₂ and VO₂ can be induced by emergency intubation and could probably explain the variable effect on oxygen extraction. Our results demonstrate that in the majority of patients subjected to emergency intubation, either septic or not, the predominant effect is to increase ScvO₂, although this cannot be predicted a priori in individual cases. Therefore, an early measurement of ScvO₂ after intubation may facilitate interpretation of further changes during ScvO₂-guided resuscitation.

Our study has several limitations. To obtain a more comprehensive physiologic interpretation of ScvO₂ changes, future studies should directly assess the effects of intubation on each of the determinants of ScvO₂. Unfortunately, we did not measure cardiac output due to the extreme emergency context. In addition, it should be confirmed if these short-term effects persist over time and if early normalization of ScvO₂after emergency intubation truly represents a correction of global hypoperfusion.

Our results should not be interpreted as a mandatory recommendation to intubate every patient presenting with low ScvO₂ during resuscitation. Some patients present severe hemodynamic instability after the maneuver. Clinicians must be aware of the inherent risks associated with emergency intubation, which should be balanced against the potential benefit.

ScvO₂ increases significantly in response to emergency intubation in critically ill septic and non-septic patients, although it is not clear if this truly represents an improvement in global dysoxia. Our findings may contribute to explain the discrepancy between EGDT trial and ICU reports concerning the incidence of low ScvO₂ values in heterogeneous critically ill patients. When interpreting ScvO₂ during early resuscitation, it is crucial to consider whether the patient has been intubated.

• ScvO₂ increased significantly in response to emergency intubation in critically ill septic and non-septic patients.

• Changes in ScvO₂ were consistent across the studied subgroups, regardless of the cause of intubation and baseline SaO₂.

• In almost 30% of the patients, this sole maneuver increased ScvO₂ to levels considered as a resuscitation goal by some current guidelines.

ALI: acute lung injury; APACHE: Acute Physiology and Chronic Health Evaluation; ARDS: acute respiratory distress syndrome; DO₂: oxygen transport; EGDT: early goal directed therapy; FiO₂: fraction of inspired oxygen; HR: heart rate; ICU: intensive care unit; MAP: mean arterial pressure; O₂ER: oxygen extraction ratio; PEEP: positive end expiratory pressure; RR: respiratory rate; SaO₂: arterial oxygen saturation; ScvO₂: central venous oxygen saturation; SOFA: Sequential Organ Failure Assessment; VO₂: oxygen consumption.

The authors declare that they have no competing interests.

GH conceived the study, and participated in its design and coordination and helped to draft the manuscript. AB conceived the study, and participated in its design and coordination and helped to draft the manuscript. RC (Rodrigo Cornejo) conceived the study, and participated in its design and coordination and helped to draft the manuscript. RC (Ricardo Castro) conceived of the study, and participated in its design and coordination and helped to draft the manuscript. MR performed the statistical analysis. JR, HP, JLN, and IA recruited patients. All authors read and approved the final manuscript.