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Print version ISSN 0034-7094On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.52 no.2 Campinas Mar./Apr. 2002
Pedro Poso Ruiz-Neto, TSA, M.D.I; Neli A. Moreira, M.D.II; Maria Elizabet Furlaneto, M.D.III
IProfessor Livre Docente da Disciplina
de Anestesiologia da FMUSP; Anestesiologista do Hospital Sírio Libanês
IIME2 do CET do Hospital Sírio Libanês
IIIMédica Geriatra do Grupo Interdisciplinar de Atendimento ao Idoso; Instituto de Ortopedia e Traumatologia do HCFMUSP; Mestranda de Geriatria Clínica - IOT-HCFMUSP
BACKGROUND AND OBJECTIVES:
Postanesthetic Delirium (PAD) is a common acute mental disorder most commonly
developed in elderly patients. Its pathophysiology is poorly understood and
PAD is often confused with others psychiatric disorders. This study aimed at
reviewing important features of this anesthetic complication in geriatric patients.
CONTENTS: Postanesthetic delirium pathophysiological mechanisms, diagnosis and treatment are described.
CONCLUSIONS: Postanesthetic delirium is a frequent and severe complication for geriatric patients. Little attention has been given to PAD and few prospective studies have been carried out. There are no available epidemiological studies on this subject in Brazil, nonetheless routine observation of geriatric patients admitted to postanesthetic care units and wards shows that PAD is a common event, suggesting the need for better preoperative assessment, adequate perioperative care and early diagnosis and treatment.
Key words: COMPLICATIONS: postanesthetic delirium
JUSTIFICATIVA Y OBJETIVOS:
Delirio pós-anestésico (DPA) es un disturbio mental agudo, que se desenvuelve
mas frecuentemente en pacientes geriátricos. La fisiopatologia del DPA es poco
comprendida y muchas veces puede ser confundido con otros disturbios psiquiátricos.
En este estudio son revistos aspectos importantes de esa complicación anestésica
en pacientes geriátricos.
CONTENIDO: Son descritos los mecanismos fisiopatológicos, diagnóstico y el tratamiento del DPA.
CONCLUSIONES: Delirio es una complicación común e importante en el pós-operatório de pacientes ancianos. Han sido relativamente negligenciado por pesquisadores y pocos estudios prospectivos han sido conducidos. En nuestro medio no hay estudios epidemiológicos disponibles, más la observación clínica diaria en las salas de recuperación pós-anestésica y enfermaría, nos muestra que la ocurrencia de DPA es frecuente, lo que nos lleva a creer en la necesidad de mejor evaluación pré-operatoria, adecuado cuidado perioperatorio y diagnóstico y tratamiento precoces.
Postanesthetic delirium (PAD) is a frequent complication, predominantly for elderly above 75 years of age. It is an acute mental syndrome caused by a diffuse brain dysfunction resulting from the synergic action of predisposing and triggering factors. It is associated to increased postoperative morbidity and mortality and prolongs hospital stay. With the increase in life expectancy in Brazil and because PAD is more prevalent in geriatric patients, the incidence of PAD is increasing during post-anesthetic recovery. It is estimated that the incidence will be even higher in the near future due to aging of the Brazilian population. This leads to the need of understanding such syndrome in order to prophylactically act on etiologic factors. This study aimed at describing PAD, its pathophysiology, prophylaxis and treatment, to prevent or early identify such syndrome.
Delirium is a syndrome characterized by consciousness disorders and cognition or perception changes not caused by previous dementia. It has an acute onset and lasts from days to weeks with fluctuating clinical course during the day. It is estimated that attention is primarily affected with the patient inattentive to the environment, unable to focus, maintain and fix attention. It is also worth mentioning the difference between delirium and hallucination. In the former there is a morbid reasoning deviation against which experience and logic reasoning are useless and where the individual gets even farther from reality surrounding him. In hallucination there is a perception deviation without real object (illusion) and is, in general, auditory. There are evidences that delirium is directly caused by physiological consequences of a general clinical condition, by intoxication, by drugs or medications, or by multiple causes.
Considering that delirium is a post-anesthetic complication, Lipowiski has classified PAD in two types, according to the onset of the complication: Emergence Delirium, appearing after anesthesia and lasting up to 24 hours after surgery; and Late Delirium, appearing after a lucid interval of one or more days 1,2.
There are two clinical PAD subtypes which may be recognized based on patients behavior or alertness:
1. Agitation or Hyperactivity-Hyperalertness
is a PAD clinical subtype characterized by Sympathetic Nervous System Hyperactivity,
increased alertness to external stimuli and psychomotor hyperactivity for days
2. Silent or Hypoactivity-Hypoalertness is a PAD clinical subtype characterized by decreased response to stimuli and introversion 1,2.
This is a didactic classification because PAD has a wider clinical spectrum where signs and symptoms may be overlapped, with post-anesthetic periods of agitation followed by lethargy 1,2.
Prospective studies with elderly patients submitted to general anesthesia have shown a 7%-14% incidence of late Delirium 1,3-6. There is a 20% to 40% incidence of Delirium in patients needing postoperative intensive care 7,8. A recent prospective study has shown a 46% incidence of delirium after aorta aneurysm surgery 3. High incidences are seen in orthopedic surgeries, especially hip surgeries. There are reported incidences varying from 17% for elective surgeries 9 to 40% and 50% for urgency surgeries 10-12. The incidence of delirium in elderly hospitalized patients varies widely 13-15, reflecting differences in age, clinical and mental status before hospitalization, different study methods (ex: prospective and retrospective) and different diagnostic criteria.
Delirium pathophysiology is not totally understood. It is considered as a neuropsychiatric manifestation of diffuse brain changes caused by brain and neurotransmitters metabolism disorders 1,2,16. It is possible that changes in neurotransmitter functions or in substances acting as neurotransmitter substrates are also involved. Acetylcholine is the most frequently mentioned neurotransmitter involved in mechanisms giving origin to delirium 17,18, because central cholinergic ways are involved in regulating attention, memory and sleep, and are very sensitive to metabolic and toxic changes 1,2. Changes in acetylcholine synthesis and release regulation may represent the common final path for several conditions (ex: hypoxia, hypoglycemia, thiamine deficiency) associated to delirium 17. There are evidences supporting this theory:
a) anticholinergic activity is increased
in delirium patients and in Postanesthetic delirium 17;
b) anticholinergic drugs are associated to acute confusional status. Physiostigmine, a cholinesterase inhibitor, although not commercially available in Brazil, has been successfully used to revert delirium 17;
c) Alzheimers patients (characterized by cholinergic transmission decrease) are particularly susceptible to delirium 17.
Other cortical and subcortical neurotransmitters seem to play an important role in regulating sleep-alertness cycle and may be related to delirium pathogenesis 17. Symptomatic delirium relief may be obtained with antipsychotics, such as haloperidol, a potent dopaminergics blocker. The reciprocity between brain cholinergic and dopaminergic activity is consistent with the increase in dopaminergics activity during delirium. Hypoxia increases intracellular dopamine concentration and decreases acetylcholine release 17. It is also known that dopaminergic drugs intoxication (ex: levodopa), often leads to delirium.
Serotonin seems to be involved in post-sepsis delirium and hepatic encephalopathy, being decreased in the former and increased in the latter. The Serotoninergic Syndrome which occurs, for instance, when serotoninergic drugs such as fluoxetine are associated to IMAO, also ratifies the participation of serotonin in the genesis of delirium. L-5-Hydroxitriptophane, a serotonin precursor, may induce delirium 17.
Gabaergic receptors are involved in delirium observed after the abrupt withdrawal of diazepinics in patients under chronic use, as well as in hepatic encephalopathy delirium 1,19.Gaba (gamma amino butyric acid) is an inhibitory neurotransmitter and the increase in gabaergic activity has been related to hepatic encephalopathy (hypoactive delirium), because high ammonia levels in this disease contribute to increase glutamate and glutamine, which are Gaba precursors.
In contrast, decreased gabaergic activity may be observed in hyperactive delirium caused by the abrupt withdrawal of sedatives or in the agitation caused by withdrawal syndrome in alcoholic patients 17.
Glutamate - another CNS neurotransmitter - release is increased as a function of acetylcholine release decrease during hypoxia 17.
Delirium has been associated to increased plasma b-endorphins levels as well as with the interruption of cortisol and b-endorphins circadian cycle 17. Glucocorticoids seem to decrase b-endorphin levels and delirium also seems to be caused by excessive glucocorticoids or withdrawal of such drug. High cortisol levels have been suggested as a possible explanation to delirium especially in stress situations such as the postoperative period 17. Anti-histaminic drugs seem to be involved in delirium, due both to acetylcholine antagonism and catecholamine and serotonin increase. Cytokines also seem to influence delirium. Alpha1-interferon changes EEG and clinical delirium manifestations 17. Subcortical structures, such as thalamus, subcortical nuclei (especially the caudate nucleus) and pontine reticular formation have an important role in delirium pathophysiology 20 because these are areas projecting their neurons to the brain cortex. It has been shown that injuries to frontal brain and basal ganglia are related to Silent Delirium, and that temporal injuries are related to Hyperactive Delirium 1,21.
RISK AND ETHIOLOGIC FACTORS
Postanesthetic delirium risk seems to be higher in elderly patients, especially above 75 years of age and with impaired physical status. Any disease, drug or drug withdrawal may lead to delirium. The presence of dementia increases the risk for delirium in approximately 3-fold 20. Parkinsons disease also predisposes to delirium 21 and drugs used to control it may also play a role. Malnourished patients, with calorie, protein and vitamin deficiencies are at higher risk for delirium 1,22. Post-mortem studies suggest that thiamine deficiency is very often overlooked in non-alcoholic patients for not presenting the classic triad of: delirium, ataxia and eye signs 1,23. Among psychiatric diseases, depression is considered a risk factor and a lot has been attributed to the anticholinergic activity of antidepressants in causing delirium 1,2,4. The role of anxiety is still controversial. Fatty embolism and brain trauma are also risk factors. Fatty embolism is an important POD cause in patients with long bone fractures or submitted to orthopedic surgeries involving bone marrow. Manifestations include: hypoxemia, fever, thrombocytopenia and delirium 1,25-27.
Many drugs are delirium triggering factors in susceptible patients. Drugs most commonly implied in triggering delirium include: narcotics, hypnotics, H2 blocker receptors, anti-Parkinson drugs and anti-cholinergic agents. Not all of them have the same potential to cause delirium. Meperidine, for example, causes more delirium as compared to other opioids due to its metabolyte - normoperidine - which has an anti-cholinergic action 20. Their delirium-inducing potential depends on above-mentioned risk factors and on individual susceptibility.
Other triggering factors are: prolonged anesthesia, metabolic disorders, infections (respiratory, urinary, hypocapnia or hypovolemia), heart disease, cardiopulmonary bypass, alcohol or benzodiazepinics withdrawal, sleep-alertness cycle changes.
It is also worth considering that aging is associated to more susceptibility to systemic diseases, to chronic drug use, to a decrease in organs and systems functional reserve, and to a decreased ability to react to stress. Sensory deficits (auditory and visual), often related to age, have been considered delirium risk factors 28.
Kidneys and liver functional reserve decrease, as well as receptors dysfunction, lead to important drug pharmacodynamic and pharmacokinetic changes in elderly people, making them even more susceptible to drug intoxication.
Physiological effects of general and epidural anesthesia on blood flow, O2 offering and brain metabolism are markedly different. Different aspects of each anesthetic technique could theoretically decrease or increase the risk for brain ischemia.
There are comparative studies in regional and general anesthesia effects on cognitive functions after non-cardiac surgeries. In a randomized study with 60 patients submitted to total hip replacement, those receiving general anesthesia presented a high level of cognitive function deterioration, but this conclusion was based on a non-standardized and subjective evaluation tool 29,30. Five other studies have not found changes in immediate or late postoperative cognitive function between general or regional anesthesia. These results, however, may be argued due to the small sample size and the heterogeneity of surgical procedures with different brain injury potential 30.
Diagnostic criteria for delirium were established by the American Association of Psychiatry in the Diagnostic and Statistic Manual for Mental Disorders (DSM) and criteria shown in chart I were listed in 1994.
Based on the criteria established by the American Association of Psychiatry, several authors have proposed delirium evaluation tools for clinical use. One of them, the Confusion Assessment Method - CAM 31 was recently validated for the Portuguese language 32. Items to evaluate delirium by CAM are shown in chart II.
The presence of items 1 and 2 plus items 3 or 4 makes up the delirium diagnosis. In the original study, it was considered that the five remaining items would not increase methods sensitivity or specificity, considered 94-100% and 90-95%, respectively.
Once the syndromic diagnosis of delirium is established, one must not forget its etiologic diagnosis. Careful clinical and lab evaluations should be performed since in theory, any unbalanced acute or chronic disease may be held responsible. Special care must be taken to identify any drug being used.
Delirium differential diagnosis includes: dementia, depression and functional psychoses. Organic disorders should also be considered, such as non-fluent dysphasia and non-convulsive epilepsy. Delirium has an acute onset with fluctuating course for days or weeks with changes in consciousness levels and marked attention deficit. Memory and orientation are often impaired. Symptoms exacerbation is common at night and at the end of the day. Cognitive changes, perception disorders, sleep-alertness cycle abnormalities and symptoms worsening at night are also seen in dementia. Although often developed in an insidious way with a trend to progressive worsening, one should nor forget that clinical dementia symptoms vary according to the etiology: for example, dementia of vascular origin may have a sudden onset; major symptom fluctuations are seen in Lewy Corpuscles Dementia, etc. A different situation leading to diagnostic confusion is the appearance of delirium in patients with a previous cognitive impairment 20,32. In this case, it is critical to obtain data about patients previous behavior and cognitive status from relatives and professionals. Any change in patients previous status should raise the hypothesis of delirium and be investigated.
Depression may mimic hypoactive delirium, with apathy, slower speech and attention and memory impairment, very often making difficult the differential diagnosis 32. In general its onset is insidious with consciousness maintenance.
Acute functional disorders may also simulate delirium, but in general they manifest in younger patients (below 40 years), alertness is maintained, symptoms do not fluctuate, hallucinations are in general auditory (in delirium they are more visual) and delirious ideas are more organized (in delirium there is disorganized thinking or loosen delirious ideas) 32.
PREVENTION AND TREATMENT
Global patients evaluation is important during preanesthetic visit, to try to document the possibility of cognitive impairment, metabolic disorders, psychoactive drugs, age, impaired socialization, infections etc. This is important for delirium support and prevention measures to be taken.
Preoperative interventions consist in treating metabolic disorders, hypoxia, dehydration, cardiovascular failure and infections, in addition to cognitive tests applied at bedside. Prophylactic multivitamin supplementation has been recommended 1,33. Anesthetic measures include hypoxia and perioperative hypertension prevention and treatment, adequate and invasive monitoring in selected patients, intraoperative and first postoperative day oxygen-therapy and avoiding anticholinergic drugs 1,34. PaO2 decrease 30 minutes after surgery and general anesthesia has been associated to delirium 24.
It is important to highlight that prevention depends on a multidisciplinary team (surgeon, anesthesiologist, nurse and general practitioner). Delirium patients should not be isolated because lack of stimulation may make the patient more introverted, with more responses to internal stimuli than to external ones 35. It is known that, in certain cases, delirium hallucinations may be treated with specific stimuli, that is, visual hallucinations through visual stimuli, auditory hallucinations through auditory stimuli, and so on 35,36. Patients room should have intermediate light, a calendar (to help orientation), and night light (lampshade). Patients wearing glasses or auditory devices should keep them 35,36. The presence of relatives is also a coadjuvant factor because they may help patients remember their homes and families, in addition to cooperating with patients observation. Patients hygiene should be preserved and diet should be adequate. Some cognitive interventions are important in handling delirium and include a clock showing the right time, calendar with current date, newspapers and magazines 35,37. Patients anxiety during lucidity due to delirium hallucinations should be explained as a transient condition 35. Pharmacological interventions are used in the acute control of symptoms while non-pharmacological measures are still being implemented. Antipsychotics are the most widely used drugs and benzodiazepinics are secondarily used for alcohol or sedatives withdrawal, or both 35,38. Haloperidol (butyrophenone) is the drug of choice. It has beneficial cardiovascular and respiratory effects and negligible anticholinergic effects. Extrapiramidal effects and malignant neuroleptic syndrome are adverse effects. Intravenous haloperidol should be used during agitations that put patient or other patients at risk.
It is to be reminded that high haloperidol doses may be associated to prolonged QT interval and to some cases of Torsades de Pointes 35,39, when therapy should be withdrawn and patient daily monitored. Droperidol may also be used, however with more sedative effect as compared to haloperidol 35.
Delirium is a frequent and major postoperative complication in elderly patients. It has been relatively overlooked by investigators and few prospective studies have been performed. It is associated to prolonged hospital stay, slower functional recovery after discharge and higher costs.
There are no epidemiological studies available in Brazil but daily observations of post-anesthetic recovery units and wards show that delirium is frequent and that better preoperative evaluation, more perioperative care and early diagnosis and treatment are needed.
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Submitted for publication April 05, 2001
Accepted for publication October 22, 2001