MOST INDIVIDUALS WHO are comatose following a traumatic brain injury (TBI) experience a period of posttraumatic amnesia (PTA)1 as they regain full awareness. The person does not recall this period afterward, although he or she may have islands of memory. Most definitions of PTA focus on an individual's disorientation in time, place and person, and/or anterograde amnesia, the inability to form new memories.2–5 Retrograde amnesia is frequently present and may persist following PTA resolution,6 while procedural or implicit memory is relatively preserved.7,8 Posttraumatic amnesia is typically considered resolved with the return of continuous memory for ongoing events.9 Memories that are well established (eg, date of birth), or require simple recognition (eg, examiner's face), recover earlier than those placing greater demand on learning of new information (eg, pictures) and day-to-day awareness (eg, day of the week).5,10–12 Posttraumatic amnesia duration is calculated from injury until return of the capacity to store and retrieve new information.13
The transient nature of PTA is thought to reflect temporary disruption of functional and structural connectivity between critical brain regions, including the posterior cingulate cortex, default mode network, frontoparietal and executive control networks involved in supporting memory, and other cognitive functions.14 Other impairments during PTA can include impaired perception, language expression and comprehension, executive function, attention and information-processing speed, and capacity.15–17 Simple attentional functions recover ahead of more complex attentional functions.16
Behavioral disturbance, particularly agitation, is also common during PTA, occurring in approximately 44% of patients.18 Characterized by disinhibition, emotional lability, aggression, impulsivity, and restlessness,18–23 posttraumatic agitation typically resolves by the end of PTA.18 McKay et al24 found that agitation increased initially as disorientation and memory began to improve, peaked, and then declined as individuals emerged from PTA. Impaired cognition appears to contribute to agitated behavior,25,26 along with environmental stimuli.27 Risk of agitation is also associated with frontotemporal lesions.28 Agitation levels are inversely associated with hospital length of stay, therapy engagement, and motor and cognitive function.21,29,30
Delusions, hallucinations, and sleep-wake cycle disturbances17,31–35 can also occur in individuals in PTA alongside generalized cognitive disturbance. Several research groups have investigated the premise that PTA should be considered as a posttraumatic confusional state16 or posttraumatic delirium, rather than an amnesic state.17,36,37 A case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group.38 Core neurobehavioral features include disturbances of attention, orientation, and memory and excessive fluctuation, and associated features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while the upper boundary is marked by significant improvement in the 4 core and 5 associated features. The INCOG team acknowledges that presence of amnesia is just one of a number of symptoms present as described in this definition of PTCS; however, the INCOG group believes that the continuing presence of disorientation and/or amnesia should be the criterion used for emergence from PTA because this is a symptom that is always present during PTA and resolves with the end of PTA. Other PTCS symptoms are not universally present and may not resolve with PTA emergence. Presence of amnesia is also the definition used in the majority of extant research. Furthermore, there are no clear criteria for determining whether a patient is in PTCS. There was also limited evidence to fully inform the natural history and upper boundary of this PTCS condition.38 Moreover, a recent survey39 indicated that most clinicians use the term PTA and utilize recovery of orientation and day-to-day memories as indicators of PTA emergence. In light of these conclusions, the INCOG panel has adopted the term “posttraumatic amnesia.”
Duration of PTA has emerged as a strong predictor of functional outcome in survivors of TBI,40–43 and is increasingly used as an index of TBI severity. Posttraumatic amnesia duration has enhanced predictive ability over Glasgow Coma Scale scores when estimating psychosocial, cognitive, and functional outcome.43–45 There have been several attempts to classify TBI injury severity or productivity outcome according to PTA duration.46–50 Posttraumatic amnesia duration measured continuously is, however, more strongly predictive of outcome, with the odds of returning to productivity declining 14% with each additional week of PTA.51 No studies have established clinically useful criteria at the milder end of the spectrum, although PTA of less than 24 hours is associated with a strong probability of return to productivity.52
Posttraumatic amnesia represents a complex and multifaceted phenomenon, the assessment and management of which pose many challenges to clinicians. The INCOG 2014 Guidelines for PTA were largely based on expert opinion, reflecting limited research evaluating methods of assessment and treatment during this recovery phase.53 As one in a series of INCOG papers, the aim of this article is to update the 2014 guidelines to better inform clinical practice in assessment and management of patients with TBI during PTA.
The reader is referred to the methods article of this series (INCOG 2.0: Methods, Overview, and Principles)54 for a review of the strategies used for the updated literature review (from 2014) and development of the recommendations and other tools. In brief, the Updated INCOG (with INCOG being an acronym standing for “International Cognitive”) Guideline follows a thorough search, review, and critical evaluation of currently published studies for each domain including principles of assessment, PTA, attention, memory, executive function, and cognitive communication. An international expert panel comprising TBI cognitive rehabilitation researchers and clinicians, most from the first version of INCOG, formed the authors. In preparation, a detailed internet and MEDLINE search was conducted to identify new published TBI and cognitive rehabilitation evidence-based guidelines (from 2014). A systematic search (2014 to July 2021) of multiple databases (MEDLINE, EMBASE, Cochrane, CINAHL, PsycINFO) was also conducted to identify TBI articles and reviews. Research articles meeting inclusion but published after July 2021 were added on the basis of the discretion of the expert panel. Two authors independently aligned the research articles within the existing INCOG guidelines and flagged areas where new guidelines may be warranted on the basis of the research evidence. This synopsis of evidence for PTA was distributed to the INCOG 2022 PTA working group. During the series of videoconference meetings, the working group examined the recommendations matrix and updated some recommendations based on new evidence, articulated novel recommendations based on the evidence available, and considered the clinical applicability of recommendations to enhance outcomes for individuals with TBI. For each recommendation, the cumulative evidence (studies used in the original guidelines and new articles) was evaluated by the panel in terms of study design and study quality to determine the level of evidence grading (see Table 1). All relevant references from 2014 were consolidated into a reference library that was made available to the author teams as they drafted the manuscript and finalized the recommendations accordingly. Consensus of the working group was reached when members unanimously agreed to the wording and evidence-grading assignment of all the recommendations. By the end, the team added 25 new references related to assessment and management of PTA for inclusion in the recommendations in this article. The clinical algorithm was updated accordingly in the management area of PTA.
TABLE 1 -
INCOG level of evidence grading system
|A: Recommendation supported by at least 1 meta-analysis, systematic review, or randomized controlled trial of appropriate size with relevant control group.
|B: Recommendation supported by cohort studies that at minimum have a comparison group (includes small randomized controlled trials) and well-designed single case experimental designs.
|C: Recommendation supported primarily by expert opinion based on their experience though uncontrolled case studies or series may also be included here.
LIMITATIONS OF USE AND DISCLAIMER
These recommendations are informed by evidence for TBI cognitive rehabilitation interventions that was current at the time of publication. Relevant evidence published after the INCOG guideline could influence the recommendations contained herein. Clinicians must also consider their own clinical judgment, patient preferences, and contextual factors such as resource availability in their decision-making processes about implementation of these recommendations.
The INCOG developers, contributors, and supporting partners shall not be liable for any damages, claims, liabilities, costs, or obligations arising from the use or misuse of this material, including loss or damage arising from any claims made by a third party.
In total, 6 management recommendations were made: 1 based on level A evidence, 2 on level B, and 3 on level C evidence. Since the first version of INCOG (2014),53 3 recommendations were added; the remainder were modified. Table 2 sets out the evidence in support of each recommendation.
TABLE 2 -
INCOG 2.0 guideline recommendations for posttraumatic amnesia and new supporting evidencea
Principles of assessment of the TBI patient
|PTA no. 1
||PTA assessment of a person with TBI should be performed daily using the Westmead Post-Traumatic Amnesia Scale until resolution of PTA (updated from INCOG 2014,53
(p310) PTA 1).
Management of patients in PTA
||Spiteri et al61
Hennessy et al62
|PTA no. 2
||To manage and minimize agitation and confusion associated with PTA, individuals with TBI should remain in a secure and supervised environment, ideally the hospital, until they have emerged from PTA.
||Carrier et al64
||Makley et al68
||Formisano et al71
||It is recommended to:
Maintain a quiet, safe, and consistent environment and avoid overstimulation
Consider the use of low-stimulation rooms
Evaluate the impact of visitors, assessment, and therapy, and limit these activities if they cause agitation or excessive fatigue
Allow rest and sleep as needed, facilitating nighttime sleep and daytime wakefulness as tolerated
Minimize the use of physical restraints to allow the person to move around freely
Have consistent healthcare professionals or trained caregivers working with the person with TBI
Establish, and utilize, the most reliable and simple means of communication
Provide frequent reassurance
Present familiarizing information as tolerated by the person
Identify and address triggers for agitation
Supervised listening to patient-preferred music may reduce agitation
Help family members understand PTA, and how to best to engage and minimize triggering agitation
||Block et al65
Park et al70
||(Updated from INCOG 2014,53
(p314) PTA 3.)
|PTA no. 3
||Physical therapists should make efforts to provide therapy to patients in PTA, while flexibly adapting session length, intensity, and location based on the degree of agitation, cognitive impairment, and fatigue of the person with TBI (INCOG 2022).
||Spiteri et al30
||Spiteri et al74
|PTA no. 4
||Swallowing and communication should be monitored by speech-language pathologists (SLPs); treating team members should use short and simple communication, while keeping repeated orientation and memory questioning to a minimum (INCOG 2022).
||Steel et al75
||Steel et al76
||Nielsen et al77
||Hart et al78
|PTA no. 5
||Individuals with TBI in PTA should receive activities of daily living (ADL) training that is standardized and follows procedural and errorless learning principles (INCOG 2022).
||Trevena-Peters et al79
||Trevena-Peters et al80
||Trevena-Peters et al81
||Mortimer et al82
Pharmacological interventions for individuals in PTA/posttraumatic delirium
|PTA no. 6
||The use of neuroleptics and benzodiazepines to treat agitation or aggression in individuals with TBI should be minimized, as these medications may slow recovery after brain injury and may have a negative effect on cognition. In general, neuroleptic medications should be limited to those given for more severe levels of agitation and aggression that threaten patient and/or staff safety. When medications are required, it is recommended to start low, go slow, and monitor the impact on agitation and cognition using standardized tools. (Updated from INCOG 2014,53
(p315) PTA 4.)
||Hicks et al84
||Phyland et al98
||McKay et al85
Abbreviations: PTA, posttraumatic amnesia; RCTs, randomized controlled trials; TBI, traumatic brain injury.
Refer to the study by Ponsford et al53
for evidence contributing to the recommendations prior to 2014.
Updated recommendations and literature review
PTA no. 1: Posttraumatic amnesia (PTA) assessment of a person with TBI should be performed daily using the Westmead Post-Traumatic Amnesia Scale until resolution of PTA (updated from INCOG 2014,53(p310)PTA 1). Level B evidence.
This recommendation has been modified from the original INCOG 2014. Given that duration of PTA is an important indicator of TBI severity and predictor of outcome, it is recommended that a validated PTA assessment tool be performed daily until PTA is resolved. Retrospective assessment of PTA duration by asking patients to recall their first memory following injury is not reliable and tends to overestimate PTA duration.55 Several standardized scales have been developed for measuring the duration of PTA prospectively, including the Galveston Orientation and Amnesia Test (GOAT),56 Orientation Log (O-Log),57 and Confusion Assessment Protocol (CAP),58 used predominantly in North America and Europe, and the Westmead PTA Scale (WPTAS),4,59,60 used predominantly in Oceania.39 A key element of the resolution of PTA is the ability to learn new information. This is acknowledged in the 2020 article by Sherer et al,38 who also recommended a need for prospective comparative cohort studies. The study by Spiteri et al61 was one such recent study that prospectively compared the 3 measures (ie, the CAP, GOAT, and WPTAS) and found that individuals with severe TBI emerged from PTA earliest on the CAP, followed by the GOAT, and finally, the WPTAS. There was good agreement between CAP and GOAT as to PTA status (the CAP includes the GOAT), but both had poor agreement with WPTAS. Among patients considered out of PTA on CAP, the majority continued to exhibit amnesia on the WPTAS and a third showed agitation at clinically significant levels.61 It would appear that the WPTAS identifies the ability to form new memories at a later stage of PTA recovery thus more clearly defining the end of PTA. The presence of ongoing amnesia and agitation, shown to resolve as the person emerges from PTA on the WPTAS, requires specialized management. Spiteri et al61 concluded that the WPTAS, administered daily, more accurately captured the full duration of PTA than the CAP or the GOAT. The CAP may provide clinicians with a broader assessment of symptoms that may or may not be present during the earlier stages of PTA (eg, agitation, sleep disturbance), and the authors of the CAP provide criteria for determining whether or not a patient is confused.38 The Working Group from the ACRM paper acknowledged that the “Assessment of cognition is limited because of failure (of the CAP) to assess verbal declarative memory. Among clinician-rated scales, agitation is better assessed using the Agitated Behavior Scale. The DRS-9 8 consists entirely of clinician-rated items, and thus the assessment may be less reliable.”38(pp8,9) Another recent study has highlighted the potential impact of opioids on WPTAS performance and clinicians should take this potential interaction into consideration when assessing PTA.62 Given the evidence and discussion mentioned previously, the INCOG team, therefore, recommends use of WPTAS as the preferred measure to determine the duration of PTA.
A very small proportion of TBI survivors remain severely amnesic and never satisfy the criteria defining end of PTA on these scales. These individuals frequently have severe and generalized cognitive impairment or preexisting impairments. Posttraumatic amnesia is rarely monitored beyond 6 months postinjury, and a decision to cease PTA testing may be made earlier than this time point.
PTA number 2: To manage and minimize agitation and confusion associated with PTA, individuals with TBI should remain in a secure and supervised environment, ideally the hospital, until they have emerged from PTA.
It is recommended to
- maintain a quiet, safe, and consistent environment and avoid overstimulation;
- consider the use of low-stimulation rooms;
- evaluate the impact of visitors, assessment, and therapy, and limit these activities if they cause agitation or excessive fatigue;
- allow rest and sleep as needed, facilitating night-time sleep and daytime wakefulness as tolerated;
- minimize the use of physical restraints to allow the person to move around freely;
- have consistent healthcare professionals or trained caregivers working with the person with TBI;
- establish, and utilize, the most reliable and simple means of communication;
- provide frequent reassurance;
- present familiarizing information as tolerated by the person;
- identify and address triggers for agitation;
- supervised listening to patient-preferred music may reduce agitation; and
- help family members understand PTA, and how to best engage and minimize triggering agitation.
(Updated from INCOG 2014,53(p314)PTA 3). Level C evidence.
This recommendation has been modified. Managing patients in the acute stages of recovery from TBI presents many challenges. Because of their confusion and agitation, they may wander or become aggressive. It is important to ensure that patients in PTA are managed in a secure and consistent environment, ideally a hospital, by people who understand their needs.
Guidelines for the management of patients in PTA have been proposed by Snow and Ponsford.63 These guidelines are based on extensive clinical experience, but there is little experimental evidence to support them. Studies of nonpharmacological interventions64,65 for agitation during PTA have design and sample size limitations. Although not used to inform the recommendations, a recent worldwide survey involving 336 clinicians working with patients in these early recovery stages is informative regarding the current state of clinical practice and potential for widespread implementation. Carrier et al66 confirmed that most clinicians follow these principles in managing agitation during PTA, with 98.7% reporting use of nonpharmacological management strategies. The most commonly used strategies were providing familiarizing information (84.8%) and environmental orientation cues (81.6%), managing patients in single rooms (81.2%), reducing noise levels (80.3%), lowering the bed closer to the floor (75.4%), using preventative strategies (74.8%), equipping the bed with safety rails (70.9%), and providing one-to-one nursing (64.7%).
Sleep disturbances are present during PTA and resolve to some degree at emergence.33,34 A recent uncontrolled study using polysomnography suggested that there was reduced slow-wave sleep and reduced sleep efficiency with increased fragmentation during PTA.35 Although the nature of the relationship between sleep quality and confusion during PTA remains unclear, research efforts have investigated the extent to which normalization of sleep-wake patterns may promote improved cognitive function.33,67 A pilot trial, with majority of participants in PTA, evaluated morning blue light combined with sleep hygiene (limited daytime napping, limited caffeine, regular sleep/wake times, controlled lighting) as compared with standard care over at least 21 days.68 Results showed no significant differences between groups in actigraphy sleep metrics, although the sleep hygiene participants showed within-group improvements in some sleep parameters (eg, total sleep time) not observed in the control group. It is unclear whether this reflected the effects of sleep hygiene measures or blue light therapy. Further studies are needed to investigate the link between sleep and confusion and evaluate sleep management interventions before specific recommendations can be made.
In the survey by Carrier et al,66 most clinicians (71.5%) reported that education about agitation after TBI was often or always provided to the patient's family and friends. However, only 52.1% felt that their own training for managing agitation was sufficient, with most relying on peer supervision. Although only 54% had access to written guidelines, those who had such access reported greater confidence in managing agitation during PTA.66 In addition to monitoring PTA status, monitoring level of agitation using the Agitated Behavior Scale20 may be helpful, particularly when introducing or grading therapies. This scale was being used by 39.2% of survey participants.66
In a recent systematic review of nonpharmacological interventions for agitation during PTA,64 music therapy had the highest level of evidence, although study quality was moderate to low. Two randomized crossover trials with high risk of bias69,70 and 1 uncontrolled case series71 found that the use of preferred live or taped music delivered for 5 to 60 minutes at the bedside daily reduced agitation. Behavioral and environmental strategies (eg, contingency management, antecedent modification, distraction, positive reinforcement) were evaluated in uncontrolled case studies and case series only but reportedly assisted in reducing agitation, particularly where the approach was flexible and patient specific.64 The harms of physical restraints were highlighted in one case study and are therefore not recommended.72
PTA number 3: Physical therapists should make efforts to provide therapy to patients in PTA, while flexibly adapting session length, intensity, and location based on the degree of agitation, cognitive impairment, and fatigue of the person with TBI (INCOG 2022). Level B evidence.
This is a new recommendation. Few studies have evaluated the efficacy of therapy provided to patients in PTA. However, existing guidelines based on similar cohorts strongly recommend that physical therapy should commence as early as possible after TBI to prevent development of contractures and maximize mobility.73 A recent cohort study by Spiteri et al30,74 showed that, although physical therapy engagement is impacted by agitation, fatigue, and cognitive impairment, it is feasible and can be effective during PTA. In this cohort study, most patients could participate in up to 1 hour of physical therapy per day, although sessions tended to be shorter when agitation and fatigue were present, or when patients were “deeper” in PTA; thus, tailoring to each person's situation is important. Most physical therapy was ward-based, with patients tolerating gym-based therapy toward the end of PTA when agitation and fatigue were resolving.
PTA number 4: Swallowing and communication should be monitored by speech language pathologists (SLPs); treating team members should use short and simple communication, whilst keeping repeated orientation and memory questioning to a minimum (INCOG 2022). Level C evidence.
This is a new recommendation. It is important that SLPs assess and monitor communication and swallowing, since cognition and behaviors, in addition to physical deficits, may place patients in PTA at risk of aspiration. The use of short, simple language is recommended to optimize safety and clarity of communication between the injured individual and others.75 Supported communication using pictures or other visual aids may be useful. Steel et al76 found that recovery of cognitive-communication deficits in 3 cases did not parallel that of PTA emergence, supporting independent monitoring, although larger studies are needed. Speech-language pathologists need to support clinical staff and families in their communication with the injured individual.77 Repeated questioning by therapists and family should, however, be kept to a minimum. Hart et al78 led a small intervention study showing success in minimizing questions demanding recall from explicit memory (eg, orientation quizzing, and personal/medical history questions), which may produce unreliable information and exacerbate frustration and anxiety in patients in PTA.
PTA number 5: Individuals with TBI in PTA should receive activities of daily living (ADL) training that is standardized and follows procedural and errorless learning principles (INCOG 2022). Level A evidence.
This is a new recommendation. A recent randomized controlled trial (RCT) by Trevena-Peters et al79 involving 104 patients with severe TBI remaining in PTA for more than 7 days in rehabilitation compared engagement in daily sessions of ADL retraining (<30 minutes) delivered following errorless and procedural learning principles in addition to usual care (ie, physiotherapy, necessary speech therapy) with usual care alone. Both groups received occupational therapy as usual following PTA emergence. The early ADL training group showed significantly greater improvement in functional independence on the Functional Independence Measure at PTA emergence and at hospital discharge. At 2-month follow-up, the group differences were no longer significant; there were no group differences on the Community Integration Questionnaire. Ninety percent of Goal Attainment Scaling goals in domains of personal care (ie, bathing, grooming, dressing, self-feeding) and light meal preparation were attained in training.80 Importantly, the ADL training did not result in increased agitation.81 An economic analysis showed that the reduction in length of stay associated with early ADL retraining resulted in average cost savings of $9654 AUD per treated patient in the base-case analysis and up to $11 481 AUD per treated patient after including savings due to reductions in hospital readmission and use of other medications.82 Clinicians highlighted benefits of therapy in PTA for therapeutic alliance, skill building, and meaningful occupation without agitation, noting fatigue as a challenge.80 On the basis of this finding, we recommend that basic ADL retraining be commenced during PTA following errorless and procedural learning principles.
In terms of cognitively oriented therapies, there is still no evidence that individuals in PTA benefit significantly from therapy to enhance orientation. Most studies to date have not controlled for spontaneous recovery. Lannin et al83 conducted a pilot RCT involving 40 patients with TBI in PTA to examine the feasibility and effectiveness of a structured reorientation program in reducing PTA duration. The program provided twice daily environmental orientation to a calendar, clock and hospital signage; a reorientation script to standardize staff and visitor interactions; and flyer to encourage visitors to simplify communication, keep visits short, and bring familiar photographs or objects. There were no statistically significant between-group differences in time to emergence from PTA on the WPTAS. Materials used in training (date, hospital) closely resembled items on the WPTAS, creating the potential for rote learning that may not reflect true PTA emergence.
Pharmacological interventions during PTA
PTA number 6: The use of neuroleptics and benzodiazepines to treat agitation or aggression in individuals with TBI should be minimized, as these medications may slow recovery after brain injury and may have a negative effect on cognition. In general, neuroleptic medications should be limited to those given for more severe levels of agitation and aggression that threaten patient and/or staff safety. When medications are required, it is recommended to start low, go slow, and monitor the impact on agitation and cognition using standardized tools (updated from INCOG 2014,53(p315)PTA 4). Level C evidence.
This recommendation has been updated. A systematic review of pharmacological interventions for neurobehavioral symptoms in PTA after TBI by Hicks et al84 identified 13 studies: 3 RCTs, 3 cohort studies, and 7 case series. In more rigorous RCTs, neither amantadine nor sertraline reduced agitation or duration of PTA. Amantadine appeared to have a positive effect on arousal in the short term. Less rigorous studies reported reduced neurobehavioral symptoms in patients administered haloperidol, ziprasidone, carbamazepine, amitriptyline, and desipramine, and varied neuroleptics, but these studies had many methodological flaws (eg, retrospective designs, lack of controls, polypharmacy). Therefore, this review provided no specific evidence-based recommendations for the use of pharmacological treatments for neurobehavioral symptoms in PTA.
Despite this lack of evidence, the survey by Carrier et al66 reported that almost 90% of clinicians indicate that pharmacological interventions are used to manage agitation during PTA in their services, of which antipsychotics (eg, quetiapine, olanzapine, risperidone), followed by anticonvulsants, antidepressants, and β-blockers, were most frequently used. McKay et al85 found that one-third of patients in one center were prescribed antipsychotics, sometimes in the absence of significant agitation levels on the Agitated Behavior Scale. These clinical practices should be noted in light of the fact that agents with strong D2 receptor antagonism such as haloperidol and risperidone are associated with impaired motor and cognitive performance.86–90 Participation in rehabilitation may also be disrupted by their deleterious side effects (eg, sedation, extrapyramidal symptoms).91 Impairments in arousal and cognition could be exacerbated by the sedating effects of antipsychotics, prolonging PTA and length of hospital stay.92–94
Unlike typical agents such as haloperidol, the atypical antipsychotic olanzapine has not demonstrated such deleterious effects on motor or cognitive outcomes90 and possesses a more favorable safety profile.95–97 In a recent placebo-controlled trial reported as an n-of-1 series,98 11 agitated participants in PTA received oral olanzapine (n = 5) or placebo (n = 6) for the duration of PTA, beginning at a dose of 5 mg/d and titrated every 3 to 4 days to a maximum dose of 20 mg/d. A significant decrease in agitation with moderate to very large effect (Tau-U effect size = 0.37-0.86) was observed for 3 of 5 participants receiving olanzapine, while no significant reduction in agitation was observed for any participant receiving placebo. However, participants receiving olanzapine showed a significantly lower mean WPTAS score, suggesting lower levels of orientation and memory during PTA and a strong trend toward longer PTA duration. Adverse events were not significantly greater in the olanzapine group and were generally mild to moderate in severity. These results suggest that olanzapine may be effective in reducing agitation during PTA, although not universally. Caution must be exercised in the use of olanzapine, however, as it may also reduce cognitive function and possibly prolong PTA. Although olanzapine appears promising for more severe agitation, the INCOG team decided not to make specific medication recommendations because of the limited research noted previously.
Figure 1 presents the algorithm of pathways for assessment and management of patients in PTA, as recommended by the INCOG team following the guideline development process.
The Audit tool items developed on the basis of the recommendations for assessment and management of PTA can be found in Table 3. Clinicians and organizational leaders are encouraged to use these tools in review or audit of individual patient charts to determine degree of adherence to the recommendations. This is most successful in changing practice when these audit results are fed back to the team for discussion of opportunities for improvement.
The recognition, ongoing assessment, and appropriate management of patients in PTA represent an important initial step in the rehabilitation process for individuals with TBI, for which there has historically been limited guidance. Since 2014, there has been growth in research investigating methods of assessment and treatment during PTA, enabling some new recommendations to be made relating to assessment measures and therapy. Six management recommendations have been made, 1 based on level A, 2 on level B, and 3 on level C evidence, of which 3 recommendations are new and others updated.
Based on new evidence, the panel is now recommending the WPTAS as the preferred PTA-screening instrument. Creating the optimal management environment that is safe, quiet, and consistent is important, with monitoring of effects of activities, visitors, and other triggers on agitation and fatigue, provided rest periods with flexible sleep opportunities, and facilitation of nighttime sleep. Use of sedation, including neuroleptics and benzodiazepines, should be minimized, and their impact on cognition and agitation monitored. Physical therapy and occupational therapy to maximize functional independence are necessary and beneficial during this phase but should be tailored according to levels of cognition, fatigue, and agitation. Speech-language pathologist assessment and monitoring of swallowing and communication are important, while avoiding repeated questioning. Cognitive assessment and therapies appear less likely to be productive. There is a continuing need for controlled trials evaluating the most effective approaches to the assessment and management of individuals in PTA. Of paramount importance is consistency of management, which may be achieved with implementation of practice guidelines such as these, and provision of education, training, and support for clinicians and families of individuals in PTA.
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