Escalation of care in a patient presenting with acute altered mental state

Opening Vignette A 75-year-old woman presented to the hospital with confusion and right-sided weakness. Her medical history included hypertension, hyperlipidaemia, diabetes mellitus (on oral hypoglycaemics) and atrial fibrillation (on bisoprolol and apixaban). She was also taking ginkgo and garlic pills as health supplements. Only limited history could be obtained from the patient. She was screened for delirium using the Confusion Assessment Method, which yielded a positive result. Physical examination revealed unequal pupils (left 4+, right 3+) and right-sided hemiplegia. Initial blood investigations were unremarkable. Stroke protocol was activated, and an urgent computed tomography of the brain was ordered.DEFINITION OF ALTERED MENTAL STATE Altered mental state (AMS) is a term used to describe a change in a patient’s baseline conscious level. Consciousness consists of two domains: content and arousal.[1] Content describes the cortical function to produce orientation, executive function and memory.[1] Arousal describes a patient’s wakefulness and ability to respond to surrounding stimuli, which is mediated by the reticular activating system.[1] Pathological processes affecting either of these structures will impair consciousness. KEY CLINICAL CONCEPT 1 General approach to altered mental state Altered mental state is not a diagnosis but a manifestation of a myriad of possible differential diagnoses [Box 1]. A systematic approach should be adopted to identify life-threatening states, followed by a comprehensive workup while avoiding over-investigation [Figure 1].Box 1: Differential diagnoses for acute AMS.Figure 1: Approach to a patient with altered mental status. ABCD: airway, breathing, circulaton and disability, EEG: electroencephalogramRapid initial assessment of ABCD Immediate assessment of the airway, breathing, circulation and disability (ABCD) should first be performed to ensure no immediate threat to life.[2] The ability of a patient to speak indicates a patent airway. In non-verbal patients, the pattern and adequacy of chest rise should be assessed to evaluate their airway and breathing. Well-felt peripheral pulses suggest an adequate systemic blood pressure (BP). The Glasgow Coma Scale (GCS) is commonly used to assess disability. An alternative assessment is the Full Outline of Unresponsiveness (FOUR) score.[3] In contrast to the GCS, there is no verbal component, thereby facilitating assessment of non-verbal patients or patients with impaired consciousness.[3] The FOUR score has been demonstrated to show good correlation with the National Institute of Health Stroke Score while providing additional assessment of brainstem function and respiratory pattern to detect herniation.[4] If there is a compromise to any component of ABCD, the patient should be resuscitated and care escalated immediately. A full set of vitals should be obtained concurrently, as they provide more clinical clues. Cushing’s reflex consists of the triad of hypertension, bradycardia and irregular breathing associated with raised intracranial pressure (ICP). Septic patients may be febrile, hypotensive and tachycardic. In stroke, hypertension may occur as a physiological response to maintain cerebral perfusion. Tachypnoea as a form of respiratory compensation may be present in severe metabolic acidosis, which can present with AMS. Hypoglycaemia, a life-threatening but easily reversible cause of AMS, must be urgently ruled out by a capillary blood sugar assay. Once an immediate threat to life has been excluded, a thorough workup should follow. History and physical examination Obtaining a history is often challenging, and a corroborative history is invaluable in these situations. This includes the patient’s baseline cognition, onset and time course of AMS. The Confusion Assessment Method is a validated tool that should be used routinely to identify delirium in patients with AMS.[5] It consists of four key features: (a) acute onset and fluctuating course, (b) inattention, (c) disorganised thinking, and (d) altered level of consciousness. A diagnosis can only be made if features (a) and (b) are present, along with either (c) or (d).[5] A history of recent head injury, seizures, headache and nausea is concerning for an intracranial event. Infective symptoms should be assessed, although occult sepsis may occur without fever or localising symptoms. Poorly controlled pain may also contribute to AMS. Additionally, a comprehensive medication review is essential. The possibility of an overdose, withdrawal and drug interaction should be considered. Common analgesics, such as morphine and gabapentinoids, have sedating side effects. Health supplements, such as ginkgo and garlic pills, are associated with the risk of bleeding,[6] including intracranial bleeds, which may manifest as AMS. A detailed physical examination is imperative since the history obtained is often limited. Evidence of organ failure, systemic infection, including meningism, and head injury should be assessed. Bite marks on the tongue and dual incontinence suggest a postictal state but these may not be present in non-generalised seizures. A full neurological examination is crucial, as the presence of focal neurological deficits is strongly suggestive of a central cause. Pupillary abnormalities may be present in brainstem dysfunction or drug intoxication. A dilated and non-reactive pupil is indicative of a third nerve palsy arising from midbrain compression.[7] Miosis can occur in opioid overdose, while mydriasis may be present in tricyclic antidepressant overdose.[7] Nystagmus may be medication-related or associated with lesions affecting the brainstem or cerebellum. Gaze deviation may be present in pontine lesions or frontal lobe lesions where the frontal eye field is located.[7] A pyramidal pattern of weakness, characterised by unilateral predominant weakness in the upper limb extensors and lower limb flexors, points to a likely stroke diagnosis. While most patients with AMS do not have stroke, 25% of stroke patients can present with AMS.[8] Recognition of raised intracranial pressure Symptoms of raised ICP are non-specific and may include AMS, headache and vomiting. A recent meta-analysis that examined the diagnostic performance of clinical findings for raised ICP found pupillary dilatation to be specific (85.9%) but poorly sensitive.[9] In contrast, a GCS score of ≤8 was sensitive (75.8%) but poorly specific,[9] suggesting that there is no single conclusive finding for a raised ICP. When brain herniation occurs, compression on the brainstem may result in cranial nerve and lateralising neurological deficits. Initial investigations Investigations should be based on clinical suspicion and reasoning rather than a ‘kitchen sink’ approach. Initial investigations should include full blood count, renal panel with electrolytes, electrocardiogram and workup for infection if clinical signs of sepsis are present. Additional tests should be guided by the possible differentials [Box 1]. These may include, where appropriate, arterial blood gas, liver function test, ammonia, B12 and folate levels, thyroid panel, serum cortisol, ketone, serum osmolality, lactate, blood cultures and toxicology screen. Neuroimaging and special tests Any patient with a recent history of head trauma, malignancy, hypertension, anticoagulation use, nausea and vomiting, new onset seizure or neurological deficits raises the suspicion of an intracranial pathology.[10] A non-contrasted computed tomography (CT) of the brain is the imaging modality of choice, as it can rapidly identify ischaemia, bleed, hydrocephalus and the presence of mass effect.[10] The CT findings of basal cistern effacement and presence of midline shift are the most sensitive indicators for raised ICP (85.9% and 80.9%, respectively).[9] In the intensive care unit (ICU), the use of invasive ICP monitoring remains the gold standard to detect rising ICP, although evidence on its impact on neurological outcomes and mortality is equivocal.[11] If the diagnosis remains unclear, a neurological consult is warranted, as specialised investigations such as a lumbar puncture (LP) or electroencephalogram (EEG) may be indicated. Analysis of cerebrospinal fluid obtained from LP may be needed to facilitate the diagnosis of meningoencephalitis, while EEG can detect the presence of nonconvulsive seizures and metabolic encephalopathies. Management and disposition The management of AMS following initial assessment involves treating the suspected underlying cause [Box 2]. Timely communication with the appropriate specialists is key, as early diagnosis and treatment can potentially maximise neurological outcomes. Haemorrhagic strokes require urgent BP control, intracranial hypertension management and possibly surgical management. Ischaemic strokes may be treated with pharmacological therapy or mechanical thrombectomy.Box 2: Management of selected causes of acute AMS.For patients on anticoagulation with intracranial bleeds, or those requiring urgent invasive intervention (e.g. surgery for source control in sepsis, neurosurgical intervention), timely reversal of anticoagulation in consultation with the primary physician and haematologist is prudent. For the critically ill who require organ support, ICU management is indicated. If an intracranial cause is suspected, management in a neuro-specific ICU has been shown to be associated with reduced mortality and morbidity compared to a general ICU.[12] KEY CLINICAL CONCEPT 2 Critical care management of worsening mental state Airway management Patients who are hypoxaemic despite oxygen supplementation, unable to maintain a patent airway, or at risk of lung aspiration will need urgent involvement of the critical care team to secure the airway. The use of a nasopharyngeal or oropharyngeal airway may help to re-establish patency in an obstructed airway, while the use of a self-inflating bag to assist the ventilatory effort will facilitate oxygenation and carbon dioxide clearance. Application of a non-rebreather mask may temporise hypoxaemia, but not hypercarbia, which is particularly detrimental in patients with suspected raised ICP. Nevertheless, it is essential for skilled personnel to assess the need for and promptly establish a definitive airway, if required. Rapid sequence induction is used for patients at risk of aspiration during endotracheal intubation. Vasopressors should be available since the use of induction agents, such as propofol, may cause hypotension, which will be deleterious in ischaemic strokes. Where intracranial bleeds are suspected, rapid- and short-acting drugs, such as fentanyl and esmolol, are ideal for titration against the sympathetic surge during intubation,[13] as the hypertensive response can potentially expand the haematoma. This is particularly crucial if the bleed arises from a ruptured cerebral aneurysm. Safe transfer to an intensive care facility Prior to the transfer to an ICU, appropriate monitoring should be applied, including BP, electrocardiogram and continuous oximetry.[13] Five-point auscultation and the presence of an end-tidal capnogram waveform confirm endotracheal tube placement. The transport ventilator, its settings and the oxygen tank should be checked prior to use. A working intravenous access should be present before transfer. Resuscitative drugs and airway equipment (self-inflating bag, intubation kit) should be available. Infusion pumps may be required to administer drugs (e.g. sedatives, antihypertensives or vasopressors) during transfer. All electronic equipment and the oxygen cylinder contents should have the capacity to last the duration of transfer. Most importantly, the accompanying personnel should be trained in equipment use and transfer of the critically ill. KEY CLINICAL CONCEPT 3 Special considerations in neuro-specific ICU Patients with deteriorating mental states often need high acuity care. Specialised neuro-intensive management targets intracranial perfusion and pressures and aims to obviate worsening injury, as these are common endpoints regardless of diagnosis. Blood pressure control to maintain cerebral perfusion In normal physiology, cerebral autoregulation maintains a constant cerebral blood flow (CBF) despite fluctuations in cerebral perfusion pressure (CPP), which ranges between 60 mmHg and 150 mmHg.[14,15] Since CPP is derived from the difference between mean arterial pressure (MAP) and ICP, MAP is commonly used as a surrogate for CPP, assuming a constant ICP.[14] In brain injury, autoregulation is impaired, causing CBF to vary linearly with MAP/CPP.[14] Consequently, a high BP can cause an increase in cerebral blood volume, worsening ICP, while a drop in BP, which compromises CPP (i.e. 1 cm. These findings were immediately communicated to the neurosurgical team, and critical care was urgently requested, as the patient became less responsive with laboured breathing and desaturation to 70% despite being on a non-rebreather mask. She was intubated with rapid sequence induction and transferred to a neuro-specific intensive care unit, where a labetalol infusion was started to maintain systolic blood pressure at 130–140 mmHg. A dose of hypertonic saline was given for midline shift. Urgent clot evacuation and decompression were performed after apixaban reversal using four-factor prothrombin complex concentrate. Postoperative Day 2 CT of the brain showed satisfactory clot evacuation and reduction in midline shift. Her Glasgow Coma Scale was E3VTM6 after sedation was ceased, and she was successfully extubated 72 h later.Financial support and sponsorship Nil. Conflicts of interest Tan TK is a member of the SMJ Editorial Board and was thus not involved in the peer review and publication decisions of this article. SMC CATEGORY 3B CME PROGRAMME Online Quiz: https://www.sma.org.sg/cme-programme Deadline for submission: 15 May 2026