Acute Onset of Impaired Consciousness

Diagnostic Evaluation in the Emergency Department

Background: Mortality in patients with acute onset of impaired consciousness is high: as many as 10% do not survive. The spectrum of differential diagnoses is wide, and more than one underlying condition is found in one-third of all cases. In this article, we describe a structured approach to patients with acute onset of impaired consciousness in the emergency department.

Methods: This review is based on pertinent articles retrieved by a selective search of PubMed and on the AWMF guidelines on the most common causes of impairment of consciousness.

Results: Impairments of consciousness are classified as quantitative (reduced wakefulness) or qualitative (abnormal content of consciousness). Of all such cases, 45–50% have a primary neurological cause, and approximately 20% are of metabolic or infectious origin. Some cases are due to intoxications, cardiovascular disorders, or psychiatric disorders. Important warning signs (“red flags”) in acute onset of impaired consciousness are a hyperacute onset, pupillomotor disturbances, focal neurologic deficits, meningismus, headache, tachycardia and tachypnea (with or without fever), muscle contractions, and skin abnormalities. Patients with severely impaired consciousness should be initially treated in the shock room according to the ABCDE scheme.

Conclusion: Acute onset of impaired consciousness is a medical emergency. Red flags must be rapidly recognized and treatment initiated immediately. Patients with severely impaired consciousness of new onset and uncertain cause, status epilepticus, lack of protective reflexes, or a new, acute neurologic deficit should be admitted via the resuscitation room.

Impaired consciousness is one of the more common reasons for presentation to an emergency department, accounting for 5–9% of patients (1, 2). The diagnosis and treatment of impaired consciousness are challenging, as there is a broad spectrum of potential underlying conditions and the need for treatment may be urgent: half of all patients receive an initial score of 3 to 5 on the five-point Emegency Severity Index [ESI] (3, 4).

The prognosis of patients with impaired consciousness is alarming: 1% die in the emergency department, and a further 10% without ever being discharged from the hospital (3).

Learning objectives

The aim of this CME article is to improve the care of patients with impaired consciousness of non-traumatic origin in the emergency department. It is focused on diagnostic aspects and a structured approach, with emphasis on the following:

• classification of “impaired consciousness” among the various disorders of consciousness;
• the differential diagnosis of acute impairment of consciousness;
• the recognition of warning signs (red flags) in patients with acute impairment of consciousness.

Terms and definitions

The term “impairment of consciousness” in this paper is used to mean reduced wakefulness (vigilance), which is also sometimes called a quantitative disturbance of consciousness. The stages of this condition have been classified as somnolence, stupor, and coma; coma is, in turn, divided into three stages (Table 1). The Glasgow Coma Scale (GCS) is used across the world as a standard means of rating impaired consciousness numerically (Table 1). The FOUR Score and other classifications have not met with similar acceptance (5). The GCS alone provides no indication of the cause of the impairment (6).

Table 1

The classification of quantitative disturbances of consciousness

So-called qualitative disturbances of consciousness are distinct from quantitative ones: they are characterized by an abnormal content of consciousness, independently of any change in wakefulness (7, 8). Qualitative disturbances of consciousness, like quantitative ones, have a broad differential diagnosis (Table 2).

Table 2

Qualitative disturbances of consciousness

Quantitative and qualitative disorders of consciousness can occur independently of each other, in alternation, or in combination (7).

According to the catalog of leading manifestations in emergency medicine issued by the Canadian Emergency Department Information System (CEDIS), acute disorders of consciousness can present in either of two ways:

• altered state of consciousness – this includes quantitative and qualitative disturbances of consciousness; and
• confusion – this is the core manifestation of qualitative disturbances of consciousness (9).

The Manchester Triage System (MTS) also provides a list of leading manifestations for initial patient assessment in the emergency department. This list does not contain any explicit category corresponding to impaired consciousness or decreased vigilance. An assessment of consciousness does, however, play an important role as a general indicator for stratifying the urgency of treatment for the leading manifestations that are listed (10). In many regions across Germany, pre-hospital patient referral codes (Patientenzuweisungscodes, PZC) are being introduced via the electronic IVENA guidance system. PZCs are determined on the basis of so-called feedback indicators entered by the emergency rescue team; in Bavaria, for example, the term “vigilance reduction/coma (without trauma)” is used for quantitative disorders of consciousness of uncertain origin, and “acute confusion/delirium” for qualitative ones. Intoxications are dealt with separately—unfortunately, as a definitive diagnosis, without specification of the clinicl manifestations. Uniform PZCs for nationwide use have not yet been established.

Differential diagnosis and general investigations

Impaired consciousness can result either from a primary neurologic disease or from secondary CNS involvement by a systemic disease. One-third of patients with severely impaired consciousness have more than one underlying cause (4). The relative frequencies of underlying causes vary depending on the patient population. The following distribution is found in large interdisciplinary emergency departments (3, 4, 7):

• 45–50% primary neurologic disease
• 20% systemic metabolic disease, including infection
• 10–20% intoxication
• 5–10% cardiovascular disease
• 5–10% psychiatric disease

A useful mnemonic for the various causes of acute impairment of consciousness is “AEIOU TIPS” (11):

A – alcohol and other intoxications

E – epilepsy, electrolyte disturbances, endocrine disturbances, encephalopathy

I – insulin

O – opiates, O₂/CO₂ (hypoxia or hypercapnia), overdose

U – uremia (metabolic)

T – trauma

I – infection

P – psychiatric emergencies, pharmacotherapy, porphyria

S – shock, subarachnoid hemorrhage, stroke, sepsis.

The patient’s history is an important guide to the differential diagnosis. Along with the information provided by the ambulance service and emergency physician, as well as by the patient himself or herself (if possible), the history should be obtained from relevant third parties (relatives, bystanders, etc.) as soon as possible, by telephone. Major crucial elements include the dynamics of the impairment, any red flags, and the patient’s prior illnesses and medications. Earlier medical reports often provide clues as well. History-taking is often limited by time pressure, and earlier medical findings are often not accessible. Indeed, the creation of a centralized and permanently accessible medical information system seems overdue particularly in view of the problems encountered in treating patients of this type.

Physical examination

After history-taking from the patient and others, a targeted physical examination should be carried out for further differential diagnosis. The indispensable components of the physical examination are the following:

• vital signs, including temperature
• Glasgow Coma Scale determination (as a baseline for comparison with possible later changes)
• examination of directed gaze, pupillomotor function, oculomotor function, and the vestibulo-ocular reflex (note: the head must not be turned forcefully in patients with possible cervical spine trauma!); corneal reflexes in patients with markedly impaired consciousness
• search for evidence that an epileptic seizure has occurred (e.g., lateral tongue bite, limb clonus)
• examination for meningismus
• motor function (limb movements, both spontaneous and in response to a painful stimulus)
• auscultation of the heart and lungs and basic abdominal examination
• search for evidence trauma (“body check”)
• inspection of the skin for rashes and/or erythema
• Initial ancillary studies

Initial ancillary studies

Certain basic ancillary studies are obligatory for all patients with acutely impaired consciousness, regardless of the suspected differential diagnosis. Among these are a blood gas analysis (BGA), including measurement of glucose and the main electrolytes, and laboratory tests including measurement of the alcohol level and, where indicated, a toxicological screen of the urine (12). Timely diagnostic imaging including the cerebral vessels should be performed (Figure).

Figure

Red flags in persistent, acute, severe impairment of consciousness

Important red flags

In addition to the long list of differential diagnoses, there are certain warning signs (“red flags”) that may indicate a life-threatening situation requiring urgent treatment (13). It is important to note that the need for multimodal acute imaging is generally not obviated by the presence of red flags, even in patients with persistent and severe impairment of consciousness (Figure); yet the recognition of important red flags can help assign priority to certain diagnostic steps (14, 15). It must also be borne in mind that red flags may be absent even in the conditions in which they are typically seen.

Red flag 1: hyperacute onset

The temporal dynamics are a vital element of the history. A hyperacute onset, i.e., the immediate development of the full clinical abnormality, indicates a probable vascular event in the central nervous system (intracerebral hemorrhage, subarachnoid hemorrhage, or basilar artery thrombosis). In patients presenting with confusion (i.e., a qualitative, rather than quantitative, disturbance of consciousness), a hyperacute onset also suggests a likely vascular event as the cause – e.g., thrombosis of the top of the basilar artery leading to peduncular hallucinosis, or bilateral impairment of the posterior circulation leading to confusion along with acute cortical blindness. Note that bithalamic infarction is often not visible in its acute phase on cerebral computed tomography with CT angiography, and possible not even on a perfusion CT.

Red flag 2: pupillomotor dysfunction

Oculomotor or pupillomotor disturbances accompanying an acute impairment of consciousness suggest the likelihood of brainstem ischemia because of basilar artery thrombosis, or else marked intracranial hypertension due to a large intracerebral or subarachnoid hemorrhage.

Red flag 3: focal neurologic deficits

Acute impairment of consciousness accompanied by a focal neurologic deficit also suggests a likely cerebrovascular event. Loss of brainstem reflexes and tetraparesis with or without pathological reflexes indicate brainstem dysfunction (hemorrhage or basilar artery thrombosis). Hemiparesis in a patient with impaired consciousness has a broader differential diagnosis including a postictal (Todd’s) paresis after an epileptic seizure, intracerebral hemorrhage, and proximal occlusion of the middle cerebral or internal carotid artery (MCA, ICA). With regard to MCA and ICA strokes, it is important for the physician to distinguish carefully between an impairment of consciousness and global (i.e., combined motor and sensory) aphasia. Aphasia of acute onset is also most likely of cerebrovascular origin, but the cause should be sought in certain vascular territories (the left middle cerebral artery or left posterior cerebral artery).

Red flag 4: meningismus

Meningismus in a patient with impaired consciousness indicates the likelihood of either meningitis/meningoencephalitis or subarachnoid hemorrhage. These two entities are distinguishable by their different temporal dynamics (rapid onset and/or thunderclap headache in the case of subarachnoid hemorrhage) and by the presence or absence of fever, elevated inflammatory parameters, or prior signs of an infection (which indicate meningitis/meningoencephalitis). The absence of meningismus, however, does not rule out either meningitis or subarachnoid hemorrhage (16). Whenever acute bacterial meningitis is a potential element of the differential diagnosis, empirical antibiotic treatment should be started immediately. In patients with markedly impaired consciousness, a lumbar puncture should be carried to obtain cerebrospinal fluid only after a CT scan of the head has been performed to rule out contraindications for the procedure.

Red flag 5: headache

A thunderclap headache reported by the patient or by accompanying persons implies a subarachnoid hemorrhage as the likely diagnosis. In patients presenting with impaired consciousness in the aftermath of a severe subacute or rapidly progressive headache, meningitis and venous sinus thrombosis should be considered.

Red flag 6: hypotension and tachypnea, with or without fever

Impaired consciousness, hypotension and tachypnea are the three elements of the Quick SOFA score, whose joint presence indicates sepsis (17) but does not imply any particular origin; in such cases, there can be either sepsis of extracerebal origin leading to impairment of consciousness, or else primary bacterial meningitis leading to systemic sepsis. If the temporal dynamics are unclear (e.g. if the patient was found after lying in his/her apartment for an unknown period of time), sepsis may be the result of prolonged recumbency in a patient with impaired consciousness, for which there may be a primary cerebral cause. Whenever sepsis is suspected, two sets of blood cultures should be obtained and empirical antibiotic treatment started.

Red flag 7: muscle contractions/myoclonus

If there are accompanying focal, generalized, or even barely detectable rhythmic muscle contractions, status epilepticus should be suspected. Non-epileptic (also called functional, psychogenic, or dissociative) seizures are a further element of the differential diagnosis.

If convulsive status epilepticus is suspected, medication should be given to terminate the seizure as soon possible. Note that epileptic seizures can also be symptomatic of a disease other than epilepsy per se, such as cerebral ischemia, intracerebral or subarachnoid hemorrhage, venous sinus thrombosis, encephalitis, or an acute metabolic disturbance.

Red flag 8: skin abnormalities

Changes in the skin can provide important clues to the cause of the disturbance of consciousness. Typical needle puncture sites above the accessible veins indicate a possible drug intoxication. Multiple petechial hemorrhages are a sign of sepsis. It is also worth taking a brief look at the palms, soles, and nail folds to check for Janeway spots, splinter lesions, and Osler’s nodes, which are characteristically seen in endocarditis.

The causes of acutely impaired consciousness are manifold (4); this is also true in patients with an initial presumed or suspected traumatic event. For example, a patient who has sustained a traumatic brain injury from a fall may have fallen as the result of an ischemic stroke (18, 19).

The management of patients with acute, severe impairment of consciousness

Patients with the new onset of severe impairment of consciousness (GCS ≤ 9) of unclear cause, status epilepticus, loss of protective reflexes, or the new and sudden onset of a neurologic deficit should be admitted via the resuscitation room. A structured, standardized registration procedure enables optimal use of the structural, organizational, and personnel resources of the central emergency department and the hospital as a whole. The staffing of the shock room team should be individually adapted to the structures of the hospital but should always include an experienced emergency physician (20). As in the trauma resuscitation room, there should be a specified team leader.

Before the structured handover of the patient from the emergency responders to the resuscitation room team, a brief orienting examination is performed to detect any acute, life-threatening disturbances requiring immediate intervention (22). The handover itself is carried out systematically and in a standardized manner, if possible without any activities on the patient occurring at the same time (23). Immediately afterwards, the patient is repositioned onto the hospital bed or stretcher, and initial care is provided according to the A-B-C-D-E scheme. The division of labor will vary depending on local structures; in-hospital emergency physicians, neurologists, internists, and anesthesiologists generally share the main responsibility. Adequate staffing and the implementation of multidisciplinary teams can optimize patient care by enabling different aspects of care to be provided in parallel.

Alarm criteria and structured treatment algorithms have long been established across Germany for resuscitation room patients with polytrauma, but there has not yet been any analogous standardized procedure for patients with acutely impaired consciousness. The recently published (PR_E-)AUD2IT scheme includes a flow chart that structures the entire process of non-traumatologic resuscitation room management, which can also be used for patients with impaired consciousness (24). This scheme is key part of the Advanced Critical Illness Life Support (ACiLS) course format, which provides a separate training concept for standardized non-traumatological resuscitation room care in German-speaking countries (25).

Special aspects

Intoxications

Intoxications are an important cause of acute impairment of consciousness; the most common offending substance in Germany is alcohol. The characteristic manifestations of intoxication with substances of any particular class are called a toxidrome (Table 3) (26). The physician suspecting an intoxication must not overlook other life-threatening illnesses that may be present; even when an intoxication seems the most likely diagnosis, an appropriate diagnostic workup of impaired consciousness is indispensable and should include blood gas analysis, laboratory tests, and brain imaging, The exception is when consciousness is seen to recover in full after the administration of an antidote. Acute intoxications are usually treated with the securing of vital functions, particularly respiration, with suitable monitoring until the manifestations of intoxication have subsided. In case of suspected non-accidental ingestion of a toxic substance, a suicide attempt should always be considered, and a psychiatrist should be consulted once the patient has recovered from the acute intoxication.

Table 3

Common toxidromes

Important non-neurologic diseases that can impair consciousness

The most common non-neurologic diseases that can impair consciousness are circulatory and respiratory diseases, infections, dehydration, and metabolic and electrolyte disorders. Impairment of consciousness by a non-neurologic disease is often more severe in persons with pre-existing (particularly degenerative) brain diseases, and in the elderly (27).

Respiratory causes (hypercapnia, hypoxia)

Hypoxia due to pneumonia, cardiac decompensation, or pulmonary embolism, if severe enough, can lead to an oxygen deficiency in the brain and thereby to impaired consciousness, up to coma. In patients with a severe, chronic disturbance of ventilation, as in chronic obstructive pulmonary disease, excessive oxygenation (usually iatrogenic, due to therapeutically administered O₂) can impair consciousness, because the CO₂ receptor_s are chronically adapted to high values, and hypercapnia, unlike in normal individuals, does not induce breathing. Rapid measurement of the arterial partial pressure of CO₂ confirms the diagnosis.

Metabolic/endocrine causes

Metabolic encephalopathies often cause both quantitative and qualitative disturbances of consciousness. The more acute the metabolic disturbance, the more pronounced the psychopathological changes. Appropriate treatment often leads to rapid and complete recovery.

The most common endocrinological cause of impaired consciousness is hypoglycemia. The diagnosis should be suspected in patients with tachycardia, hypertension, sweating, and agitation or other disturbances of consciousness up to and including coma and generalized seizures. If the point-of-care meter does not show a normal blood glucose level, glucose (and thiamine) should be given intravenously at once to treat possible hypoglycemia without any further delay.

Impaired consciousness due to liver failure is called hepatic encephalopathy. Patients often manifest a (flapping) tremor, hyperreflexia, and reduced wakefulness. The diagnosis is confirmed by laboratory testing of liver function, the clotting system, and the serum ammonia level. Renal failure can also impair consciousness.

The clinical manifestations of adrenal insufficiency are hypotension, (pseudo-)peritoneal signs, and abdominal pain, along with adynamia and impaired consciousness. In patients with any of these manifestations, possibly accompanied by hyponatremia and/or hyperkalemia, an Addisonian crisis should be suspected and hydrocortisone administered immediately.

Electrolyte disturbances

Electrolyte disturbances can cause marked CNS dysfunction and severe impairment of consciousness. Hyponatremia is the most common cause. The main manifestation of hypercalcemia is an impairment of consciousness, possibly accompanied by polyuria and dehydration. In hypocalcemia, the muscle tone is increased. There are no sharp electrolyte thresholds for the appearance of neurological abnormalities; the manifestations are generally worse the more rapidly the electrolyte disorder has arisen.

Infections and sepsis

Impaired consciousness due to sepsis is common and is called septic encephalopathy. The likelihood of encephalopathy in sepsis rises with age. Its severity is correlated with the extent of sepsis. Wakefulness is one of the three clinical parameters of the Quick-SOFA (qSOFA) score (respiratory rate > 22/minute, new onset of impaired consciousness, systolic blood pressure < 100 mm Hg): if two of these three items are present, sepsis must be considered. The qSOFA is neither sensitive nor specific for sepsis, however, and therefore the new sepsis guideline does not recommend its use as a sole screening tool (28). In elderly patients with neurodegenerative diseases, local infections without systemic sepsis often suffice to cause a quantitative or qualitative impairment of consciousness.

Diagnostic considerations for transient impairment of consciousness

Many patients presenting with impaired consciousness as their main problem have already regained consciousness or improved to a marked extent by the time they arrive in the hospital. Despite any such improvement, however, patients who have had a transient impairment of consciousness must still undergo a thorough diagnostic assessment in the emergency department: serious illnesses and conditions requiring urgent treatment must not be overlooked, and only a secure diagnosis enables subsequent resource-optimized care on a suitably specialized hospital ward, or—in the event of discharge—by a specialist in the ambulatory setting.

The following entities, in particular, must be distinguished from each other in patients with transiently impaired consciousness:

• epileptic seizures,
• syncope, and
• psychogenic non-epileptic seizures.

Differentiation can be difficult in individual cases, but there are often clues to the cause (Table 4).

Table 4

The differentiation of transient impairment of consciousness

Generalized tonic-clonic epileptic seizures

In patients with known epilepsy presenting with seizures, further treatment can generally be provided in the ambulatory setting once critical triggers such as hyponatremia and infection have been ruled out. Patients presenting with their first-ever epileptic seizure without any known cause need an extensive differential-diagnostic evaluation, often best done on an inpatient basis (29).

Syncope

An initial diagnostic classification should be made in the emergency department (30). In case of vasovagal or orthostatic syncope, further diagnostic evaluation and treatment can be provided in the ambulatory setting. A cardiopulmonary cause, or syncope due to hypovolemia/hemorrhage, calls for admission to the hospital. If the cause of syncope is unknown, individual risk stratification should be performed (31).

Psychogenic non-epileptic seizures (PNES)

Benzodiazepines are not recommended for the treatment of psychogenic non-epileptic seizures but are often given anyway, particularly while patients are on their way to the hospital (usually because their seizures are presumed to be epileptic). In one-third of patients with functional seizures, benzodiazepines do not halt the seizure-like motor activity (32). The key to distinguishing epileptic from psychogenic non-epileptic seizures is a thorough neurological examination combined with a detailed medical history (trigger situations, prior medical findings).

If a young patient reports a “blackout” (often while at a party), knockout drops—usually gamma-hydroxybutyrate—must be included in the differential diagnosis of temporarily impaired consciousness. Other causes of self-limited transient impaired consciousness that should be considered include transient ischemic attacks of the posterior circulation, subarachnoid hemorrhage, and metabolic causes, but these are unlikely in the absence of other accompanying symptoms. If the patient has fallen during a temporary impairment of consciousness, injuries due to the fall must be ruled out, with further diagnostic studies if necessary.

Overview

A wide variety of neurological, general medical, and psychiatric illnesses may lie behind the clinical picture of acutely impaired consciousness. The appropriate management of these patients is an interdisciplinary challenge. It should ensue without delay with the collaboration of emergency physicians, neurologists, and internists.

Conflict of interest statement
The authors declare that no conflicts of interest exist.

Manuscript received on 18 December 2023, revised version accepted on 17 April 2024.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Matthias Klein

Zentrale Notaufnahme, Klinikum der Ludwig-Maximilians Universität (LMU)

Marchioninistr. 15, D-81377 Munich, Germany

Cite this as:
Weiglein T, Zimmermann M, Niesen WD, Hoffmann F, Klein M: Acute onset of impaired consciousness: diagnostic evaluation in the emergency department. Dtsch Arztebl Int 2024; 121: 508–18. DOI: 10.3238/arztebl.m2024.0079

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