Risk factors and outcomes after unplanned extubations on the ICU: a case-control study

Unplanned extubation (UE) is a frequent event after endotracheal intubation for respiratory support in critically ill patients and is associated with increased morbidity and mortality [1‐12]. The incidence of UE among intubated patients is reported to vary from 0.3% [7] to 14% [7, 13], depending on patient characteristics, the characteristics of the intensive care units (ICUs) surveyed and the duration of mechanical ventilation of the patients [14]. UEs account for approximately 10% (range, 3% to 16%) of extubations and require reintubation in 60% of the cases [4]. Furthermore, experiencing an UE is associated with prolonged duration of mechanical ventilation, ICU stay and hospital stay compared to not having experienced an UE [4, 15, 16]. Reported risk factors for UE include route of tracheal intubation, method of tube fixation [3] and method and level of sedation [3, 17].

Unplanned extubation is defined as a premature removal of the endotracheal tube by action of the mechanically ventilated patient (deliberate unplanned extubation) [17] or premature removal during nursing and medical care (accidental extubation) [18]. Although UE has been studied regularly, many questions about incidence, determinants and outcomes of UE have not been answered in all detail. Moreover, inconsistent findings exist, especially with respect to outcomes after UE, with some authors reporting improved outcomes after UE [14, 15]. This may be explained by differences in study design, study population and ICU characteristics.

Understanding the determinants of UE is critical for risk assessment in individual patients and for developing interventions to reduce the incidence of this mechanical ventilation complication. We therefore aimed to study the incidence, determinants and outcomes of UE and to asses the risk factors for reintubation in full detail. The tertiary care ICU setting in which this case-control study was performed represents the full spectrum of clinical problems in contrast to other studies. Furthermore, we were able to obtain extensive clinical information for cases and controls from automated clinical data registers.

This study has shown that UE occurred in 2% of all mechanically ventilated patients. Being awake or being agitated (Ramsay Sedation Scale scores 1 and 2, respectively), use of midazolam and being admitted to a specific ICU subunit were associated with an increased risk for UE. Analysis demonstrated that patients with an UE without subsequent need for reintubation had lower ICU and hospital mortality than mechanically ventilated controls and UE patients in need of reintubation.

In the present study, we used a case-control design, which was also used in some other studies [1, 5, 15, 17, 18]. The case-control design enables researchers to study the relationship of multiple factors for one outcome and is especially appropriate for studying infrequent outcomes, such as UE. However, the selection of controls is crucial for a case-control study. The control group should be a random sample of all patients who were at risk of experiencing the studied outcome. In the present study, the control group was sampled from all other mechanically ventilated patients admitted to the ICU at the time of an UE. These patients are in principle at risk for an UE and represent the distributions of risk factors that will be compared to the distribution of risk factors in the cases, with respect to the level of sedation. Both cases and controls had a Ramsay Sedation Scale score vary from 1 to 6, pointing toward the appropriateness of the control group. We applied density sampling, and control patients were matched on time. Consequently, it was possible that a patient served as a control twice. Nevertheless, at both time points, the control patients were truly representative of the population from which the case arose and were comparable to the case of that time point.

The reported incidences of UEs differ largely, ranging from 0.3% to 14% [7, 10, 13, 15, 18]. These incidence levels are difficult to compare because of differences in the calculation method used for data collection in the various studies. Furthermore, the incidence variation can be partially explained by the heterogeneity of the studied ICU population [14]. The incidence of UEs in our ICU was relatively low (2.1% for mechanically ventilated patients and 0.4% per ventilation day). This can partly be explained by the high nurse-to-patient ratio in our hospital. It is unlikely that underreporting is responsible for the low incidence, since in our institution parallel incident reporting systems at the ICU are used to minimize this effect. Furthermore, extensive attention was given to the implementation and execution of the study.

Male sex and subunit ICU were risk factors for UE. Remarkably, not only agitation and restlessness (Ramsay Sedation Scale score 1) predisposed patients to UE, but also normal consciousness (Ramsay Sedation Scale score 2) was highly associated with UE. Our findings are consistent with those reported by other authors [1, 11, 13, 17, 18, 23, 24]. The observed agitation and restlessness could well be the clinical manifestations of delirium. We were capable of investigating all medication use (narcotics and analgesics) at the time of UE by means of the electronic medical records. The proportion of patients who received sedatives and narcotic analgesics was similar between the two groups. In the univariate model, we found that the medication administered to decrease agitation and delirium actually increased the risk of an UE. In the multivariable model, midazolam was associated with an increased risk of UE. A possible explanation is that midazolam is known for its paradoxical reaction [25] and is also associated with delirium in ICU patients [26]. Furthermore, the relationship could be confounded by the facts that agitated patients were more frequently treated with midazolam and we were unable to completely correct for agitation. To get more insight into this process, a future randomized, controlled trial has to be established that could focus on the dose-response relationships and on goal-directed medication use. The ICU subunit with an increased risk for UE distinguishes itself by a somewhat higher admittance rate of postoperative cardiosurgical patients. It is known that this patient subgroup is more likely to be agitated after surgery [27]. Although we corrected for type of patient (medical, surgical or thoracic surgical), this could be the explanation for the subunit effect. Factors that might have been a clarification in terms of subunit culture or care were not systematically collected and therefore were not examined.

Previous studies [1‐12], particularly before 2000, showed that UE was associated with a higher risk for prolonged duration of mechanical ventilation, increased ICU stay, increased hospital stay and increased mortality. In the present study, patients with an UE had better outcomes than control patients. This finding is not yet very well established in the literature on UE, although we are not the first investigators to report it. Epstein et al. [5], Krinsley and Barone [15] and Bouza et al. [14] also found that the outcome after an UE was than that of patients without UEs. A first explanation could be that UE patients are in better clinical condition, more alert, physically stronger and able to extubate themselves. Although it is not obvious from the baseline characteristics (Table 1), we cannot exclude that this explanation is valid. Second, earlier UE could result in shorter duration of mechanical ventilation and ICU length of stay and thus in fewer complications and improved outcomes. The improved outcomes of the UE patients not needing reintubation is in accord with this hypothesis. Only a few other authors [5, 14‐16] have described outcome differences between patients with UE with a subsequent need for reintubation and patients with UE not needing a reintubation. Krinsley and Barone [15] and Bouza et al. [14] were the first to describe better outcomes for patients who experienced an UE and did not need reintubation.

Another explanation for the improved outcomes is that patients at our ICU are systematically intubated longer than they need to be. We do not know at what time patients with UEs would have had their planned extubations, but we hypothesized that the extubation success rate of the overall ICU population might provide additional insight. We have calculated our historic extubation success rate. In accordance with other reports in the literature, we defined the extubation success rate as the proportion of patients in whom it was unnecessary to reinstitute ventilatory support within 48 hours after planned extubation [28]. Over the study period (1 January 2005 to 1 June 2008), we found that of 4,710 patients, 931 needed reintubation within 48 hours after planned extubation, resulting in an extubation failure rate of 19.8% and an extubation success rate of 80.2%. These data could suggest that a proportion of our patients were indeed intubated longer than they needed to be despite our weaning protocol, therefore putting them at increased risk of UE. Maybe because it is not explicitly stated in our protocol how often patients should undergo a SBT, the SBT is not applied as frequently as it should be to select patients who are eligible for extubation. Another hypothesis is that the medical and nursing staff are still reluctant to perform extubation despite the use of a weaning protocol. Awareness and education with respect to the weaning protocol and more explicit discussion of the frequency of SBTs could decrease this reluctance to perform extubation and thereby reduce the length of mechanical ventilation time and maybe minimize the UE rate [1, 2, 18, 29, 30].

With respect to the UE patients who needed reintubation, it can be stated that in our institute, a protocol for intubation and the start of mechanical ventilation is applied with the following intubation criteria: (1) upper airway obstruction, (2) respiratory failure due to exhaustion, (3) impaired or decreased level of consciousness, (4) cardiopulmonary arrest and (5) need for sedation for diagnostic or therapeutic procedures. The fact that 90% of the reintubated UE patients needed reintubation within 1 hour is in agreement with the risk factors for reintubation (high PEEP, respiratory frequency for UE, delirium during ICU stay and respiratory problems during ICU stay).

Some studies [1, 13, 18] have developed a clinical risk stratification tool to identify patients at risk for UE. These tools are based mainly on significant sedation and the consciousness level of the patient. Our study observed additional risk factors. If patients are identified as having a high risk for UE, temporarily intensified surveillance may be needed and extubation should be performed as soon as possible. ICU staff could take additional preventive measures (for example, preventing agitation, adjusting clear fixation policy, enforcement of 24-hour bedside supervision). These new policies will be an important area for further research investigations.

ICU patients who experienced an UE did not have increased mortality. Moreover, following an UE, patients not needing reintubation had significantly better outcomes than reintubated patients. Male sex, subunit ICU, agitated or awake consciousness and use of midazolam at the time of UE were identified as risk factors for an UE.