Central Nervous System Risk Assessment: Preventing Postoperative Brain Injury

Definition

Postoperative delirium (POD) is an acute confusional syndrome that is frequently encountered in the postoperative setting. In fact, it is the most common surgical complication among older adults, with an incidence ranging from 15% to 50% in this population, depending on the procedure. Delirium can be defined as an acute, fluctuating, multifactorial disorder characterized by a decline of attention, cognition, and awareness, and it is a distinct disorder that is separate from dementia or chronic cognitive decline. Three subtypes of delirium exist: hyperactive, hypoactive, and mixed. Despite hypoactive being the most frequent subtype, patients who have hypoactive delirium are less frequently diagnosed and have poorer prognoses than those with hyperactive delirium. Unfortunately, a diagnosis of delirium carries many implications for a patient because those diagnosed with delirium have increased morbidity, mortality, loss of independence, likelihood of subsequent institutionalization, and health-care costs.

Establishing a diagnosis of delirium requires that the patient’s baseline mental status be defined with a preoperative screen or by a knowledgeable informant. Once this is established, a cognitive screening test may be used to determine what, if any, change from baseline the patient is experiencing. There are many different diagnostic tools and severity scales for delirium, with two of the most common being the Confusion Assessment Method (CAM) and CAM-ICU, which is a derivative of the CAM that is intended for mechanically ventilated patients in the intensive care unit (ICU) ( Fig. 7.2 ).

Risk Factors

The pathophysiologic mechanisms underlying delirium are poorly understood and may include neurotransmitter imbalance and/or neuroinflammation. Despite the lack of a definite cause of delirium, multiple predisposing and precipitating factors for delirium have been elucidated ( Table 7.1 ). The summation of predisposing and precipitating factors will determine a patient’s likelihood of developing delirium; a higher burden of predisposing factors will necessitate a lower number of precipitating factors. Multiple drugs have been shown to increase the probability of delirium in the geriatric population and should be avoided in the perioperative period if possible. These include benzodiazepines, anticholinergics, diphenhydramine, hydroxyzine, meperidine, histamine-2 antagonists, and sedative hypnotics.

Intraoperative Management

Currently, optimal intraoperative management of patients at risk for delirium is not yet well defined. The only intraoperative delirium-reducing interventions for which strong recommendations exist are avoidance of predisposing drugs and adequate pain control, with nonopioid medications and regional anesthesia being a consideration when possible or appropriate. However, several interventions are currently being investigated. Some studies have shown that deeper levels of anesthesia are associated with increased incidence of POD and that bispectral index (BIS)-guided anesthetics are associated with a lower incidence of POD. It has been hypothesized that BIS-guided anesthetics may have fewer periods of electroencephalogram (EEG) burst suppression. However, the increased burden of burst suppression and other EEG patterns identified in patients with POD may simply be a marker of fragility and not a causative factor. The largest randomized trial to date, the ENGAGES [Electroencephalography Guidance of Anesthesia] trial, randomized over 1200 patients to EEG-guided anesthesia or control and found no difference in the incidence of POD. Other studies are ongoing.

Another intervention that has been investigated in recent years is the use of dexmedetomidine. Recent studies have shown that dexmedetomidine administered perioperatively as a low-dose prophylactic infusion may decrease not only POD but also the rates of stroke and both operative and in-hospital mortality. These findings may be explained in part by evidence that dexmedetomidine acts via the JAK2/STAT3 pathway to attenuate isoflurane-induced neurocognitive deficits in senile mice. However, other studies have been unable to replicate these findings and have found that dexmedetomidine does not decrease POD. A recent report found that low-dose nocturnal dexmedetomidine reduced POD in the ICU, but this awaits validation in larger trials. As the data are conflicting at this time, it would be reasonable for the anesthesiologist to consider the perioperative use of dexmedetomidine in the at-risk patient if it is considered clinically feasible/appropriate. It remains unclear whether intraoperative, postoperative, or combined dosing is most effective.

Much like dexmedetomidine, ketamine showed initial promise as an intraoperative intervention to prevent POD. However, a recent study was unable to replicate this result, and patients receiving ketamine experienced higher incidences of hallucinations and nightmares (but not delirium). Although ketamine does show benefit in decreasing delirium in children, there are still relatively few studies examining ketamine in adult delirium prevention. Ketamine may allow lower perioperative opioid doses to be used, and the anesthesiologist may still consider ketamine use in at-risk patients as part of a multimodal anesthetic.

Finally, both cholinesterase inhibitors such as rivastigmine and antipsychotics such as haloperidol administered perioperatively in a preventative capacity have been investigated. Cholinesterase inhibitors have not been found to decrease delirium incidence and furthermore may be associated with increased adverse effects, including mortality. It is not recommended that patients not taking preoperative cholinesterase inhibitors be started on one in the perioperative setting. Data on prophylactic perioperative use of antipsychotics are less conclusive but generally do not favor their use, owing to mixed results on delirium prevention, no decrease in mortality, and a high rate of adverse effects.