Agitation During Prolonged Mechanical Ventilation and Influence on Weaning Outcomes

Fig. 34.1

A temporal view of agitation and weaning of mechanical ventilation

According to the new classification of weaning given at the Consensus Conference, there are three different groups of patients [23, 24]. In the group of patients with simple weaning, the role of agitation is minor. Agitation and delirium play a relevant role as cause or contributors for patients with difficult and prolonged weaning, but studies of this association are scarce compared with more-studied mechanisms such as the respiratory pump or cardiovascular dysfunction as etiologies of weaning failure. In patients with prolonged weaning, most times there are two or three different associated factors. Delirium is frequent in that group of patients, and sometimes a severe agitation requires restarting sedatives while neuroleptics are started. This obviously means a delay in doing a SBT (weaning test) because adequate mental status is a criteria for a SBT. In addition, an “adequate mental status” is a bit ambiguous and clinically there are a gradients from a hypoactive delirium to severe agitation. To prevent the impact of a new deep sedation on the capacity to do the next SBT, the election of sedative and/or antipsychotic to treat delirium and agitation at this time is relevant, as will be discussed below.

Agitation is one of the subjective criteria for failure of a SBT; however, agitation is a continuum, with mild and severe types, and sometimes isolated mild agitation can be controlled with nonpharmacological measures and medication. However, in other cases a new agitation during a SBT is a symptom of cardiovascular or respiratory failure and the patient must be reconnected to MV This difference is not always easy to detect and it requires a global evaluation of whether mental symptoms of failure are alone or with other objective or subjective failure criteria. There are no studies to help to make this decision and a good clinician is needed.

Sometimes agitation begins following extubation. Extubation failure happens in 6–18 % of patients and is associated with increased ICU mortality, so it is important to detect it and to quickly determine whether the patient needs to be reintubated. Similar to agitation during SBT, the new agitation after extubation is a bad sign and, after a global evaluation for other criteria of failure, the decision must be made whether to offer noninvasive ventilation (NIV) or a fast reintubation. In our opinion, significant agitation is in this setting a contraindication for NIV. Only in mild agitation without other signs of failure can we offer NIV with close observation.

The incapacity to follow orders has been studied in neurocritical patients as a risk factor for extubation failure [25], but another more recent study did not show an association between delirium and extubation failure [26]. This research area looks controversial and more studies are needed looking for the association of delirium and/or agitation with extubation failure.

34.5 Preventing and Managing Agitation

The following measures are recommended to prevent agitation (Table 34.1):

Table 34.1

Key elements for the prevention of agitation in MV patients

(a)	Make a proper anamnesis, with emphasis on assessing risk factors
(b)	To implement serial monitoring the presence of pain, sedation, and agitation levels
(c)	Monitoring of delirium at least twice a day
(d)	A protocolized pharmacological and nonpharmacological management of pain and delirium
(e)	To consider the use of dexmedetomidine as sedative of choice, or as coadjuvant if agitation during weaning

(a)

Complete history of risk factors for agitation, including medication list and history of illicit drug, alcohol, or tobacco use.

(b)

Serial evaluation or pain, using instruments validated for mechanically ventilated patients such as the behavioral pain scale [27] or the Critical-Care Pain Observation Tool (CPOT) [28].

(c)

Serial monitoring of sedation level and agitation using the SAS or RASS, mentioned above. Chanques et al. [29] reported that systematic monitoring for pain and agitation alone reduced the incidence of agitation.

(d)

Daily monitoring of delirium. As with pain, sedation, and agitation, valid instruments should be used to monitor delirium, such as the Confusion Assessment method for the ICU (CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC) scales.

(e)

Adherence to recommendations for pain and delirium management. Severe pain is also recognized as a causal factor in agitation; therefore, optimal analgesia is important. To manage hypoactive delirium, early intervention with nonpharmacological therapy should be deployed, including occupational therapy and multimodal management.

(f)

Use of dexmedetomidine as a sedative in MV patients. There is evidence from clinical trials as well as level IIB evidence suggesting that dexmedetomidine reduces the risk of delirium compared with benzodiazepines. Given that delirium is the main cause of agitation, it is reasonable to assume that reducing the incidence of delirium may reduce the incidence of agitation, although this idea has not been systematically evaluated.

34.6 Treating Agitation

At onset of agitation, the first priority is to minimize risk to the patient’s physical integrity (falls, accidental removal of breathing tube, catheters, drains, or other equipment), and, in parallel, to protect the hospital staff from physical injury. Severe agitation in a young patient may require the strength of three or four team members to apply physical restraints.

It is crucial to evaluate the severity of the condition, as appropriate management of mild cases can often prevent the onset of severe agitation. Mild cases will respond to verbal direction, allowing time for appropriate diagnostic and pharmacological intervention. The diagnostic process should also include evaluation of pain, delirium, and withdrawal syndromes, as previously noted. If these scales suggest the presence of pain, an opiate bolus is recommended; in our center, we use 25–100 μg of fentanyl, depending on body weight, titrating according to clinical response. If CAM-ICU or ICDSC scores indicate delirium, the use of neuroleptic agents is recommended. Worldwide, the most commonly used drug of this type is haloperidol. The recommendation is to begin with 0.5–1.0 mg administered enterally, keeping in mind that the onset of action is about 20 min. Intravenous administration is discouraged, due to the higher risk of prolonged QT interval and arrhythmias. If no other administration route or drug is available, we suggest using 0.5–1 mg of intravenous haloperidol in 50–100 of saline over 30 min, performing an electrocardiogram as soon as possible to evaluate for QT. It is important to consider that neuroleptics have potential adverse cardiac and neurological effects (such as extrapyramidal symptoms), and the level of evidence supporting their use is low.

Given their more favorable safety profile, recent studies have evaluated atypical neuroleptic agents such as risperidone, quetiapine, and olanzapine. One small-scale study of the use quetiapine in critical care patients suggested a reduced duration of delirium as compared with a control group [30].

For more severe cases, a bolus of sedative may be necessary during the acute phase to control agitation.

Dexmedetomidine should be considered the sedative of choice for managing agitation during weaning. The goal is not only to control agitation but also to avoid returning to profound levels of sedation that would delay or limit the application of the SBT. Dexmedetomidine is a promising candidate for this application due to its characteristics, although, again, evidence for its use is limited to clinical series and extrapolations from clinical trials comparing this drug to benzodiazepines as the sedative of choice during weaning [31–33].

Other therapeutic strategies that have been studied at the level of clinical series or small clinical trials include music therapy and electroconvulsive therapy in refractory cases.

34.7 Conclusion

Agitation is common among mechanically ventilated patients, typically occurring during the weaning period. Agitation limits both the application and the likelihood for success of the SBT and increases the chance of weaning failure. In addition to accurately diagnosing agitation, it is important to measure the severity of the condition and monitor for etiologies other than delirium. Using best practices for managing pain, sedation, and delirium improves outcome and reduces the impact of agitation during the weaning process.

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