UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New series No 309 - ISSN 0346-6612
'
From th e D epartm ents of G eriatric M edicine and In te rn a l M edicine, U niversity of Umeå, and th e D epartm ent of G eriatric M edicine, K arolinska In stitu te , Stockholm , Sweden.
ACUTE CONFUSIONAL STATE (DELIRIUM)
Clinical stu d ie s in h ip -fractu re a n d stro k e p a tie n ts
iy
Yngve G ustafson
Umeå 1991
UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New series No 309 - ISSN 0346-6612
From the D epartm ents of Geriatric Medicine and Internal Medicine, University of Umeå, and the D epartm ent of Geriatric Medicine, Karolinska Institute, Stockholm, Sweden.
ACUTE CONFUSIONAL STATE (DELIRIUM)
C linical stu d ies in hip-fracture and stroke p atien ts
AKADEMISK AVHANDLING
som med vederbörligt tillstånd av R ektorsäm betet vid Umeå universitet för avläggande av doktorsexam en i m edicinsk
vetenskap kommer a tt offentligen försvaras i Tandläkarhögskolan 9 trp sal B, i Umeå lördagen
den 8 ju n i 1991 kl 10.00.
Yngve Gustafson
Umeå 1991
ABSTRACT
ACUTE CONFUSIONAL STATE (DELIRIUM).
Clinical studies in hip-fracture and stroke patients.
Yngve G ustafson, D epartm ents of Geriatric Medicine and Internal Medicine, Umeå University, Umeå, Sweden. D epartm ent of G eriatric Medicine, Karolinska Institute, Stockholm, Sweden.
Acute confusional state (ACS) or delirium according to DSM-III-R holds a central position in the medicine of old age. ACS is a common and som etim es the only symptom of diseases and medical com plica
tions in the elderly patient.
The aim of this study was to elucidate ACS in p atien ts w ith femoral n eck fra c tu re s an d p a tie n ts w ith acu te stroke w ith reg ard to frequency, predictors, possible pathogenetic m echanism s, associated complications, assessm ent and docum entary routines and the clinical outcom e for the patients. An intervention program to prevent p o st
operative ACS based on our results was developed and evaluated.
The m ain findings of the stu dy were high frequencies of ACS in elderly p atien ts with femoral neck fractures (61 %) and in p atien ts w ith acute stroke (48 %). The main risk factors for ACS in p atien ts w ith femoral neck fractures were old age, diseases and drug tre a t
m ent interfering with cerebral cholinergic metabolism. There was no link betw een anaesth etic technique and ACS b u t the connection betw een peroperative hypotension, early postoperative hypoxia and ACS was close.
In stroke patien ts the degree of extremity paresis and old age were in d ep en d en t ACS risk factors. ACS was commonly associated with p ost stroke complications such as myocardial infarction, pneum onia, u rin ary infection and urinary retention. In stroke patients there was a close connection between high hypothalam ic-pituitary-adrenal axis (HPA-axis) activity and ACS. High HPA-axis activity and disturbances in th e cerebral cholinergic system may be two im p o rtan t ACS m echanism s.
A correct diagnosis is a prerequisite for proper tre a tm e n t of ACS and its underlying causes. In the orthopaedic w ards both physicians an d n u rs e s diagnosed and docum ented ACS poorly and therefore associated complications were insufficiently treated.
The intervention program for postoperative ACS, aimed m ainly at p ro te c tin g th e cerebral oxidative m etabolism an d th e re b y th e cereb ral cholinergic m etabolism w hich is especially sensitive to hypoxia. Postoperative complications associated with ACS were also treated . The intervention resulted in reduced frequency, d u ratio n and severity of postoperative ACS and in shorter orthopedic ward stay for p atien ts with femoral neck fractures.
Key words: Acute confusional state, delirium, elderly, stroke, femoral neck fractures, acetylcholine, cortisol.
UMEÅ UNIVERSITY MEDICAL DISSERTATIONS
New series No 3 0 9 - ISSN 0 3 4 6 -6 6 1 2 From the Departments of Geriatric Medicine and Internal Medicine, University o f Umeå, and the Department of Geriatric Medicine, Karolinska Institute, Stockholm, Sweden.
ACUTE CONFUSIONAL STATE (DELIRIUM)
Clinical stu d ies in hip-fracture and stroke patien ts
Yngve Gustafson
A l v
Umeå 1991
Copyright © 1991 by Yngve Gustafson ISBN 91-7174-594-7
Printed in Sweden by LARSSON & CO:S TRYCKERI AB
Umeå 1991
‘To my ÿamity
C O N T E N T S
Abbreviations 6
Abstract 7
Original papers 8
Introduction
History 9
Term inology 9
Diagnostic criteria 11
Clinical Features 13
Differential diagnosis 14
ACS frequency 16
Postoperative ACS 17
ACS in stroke patients 18
Predisposing ACS factors 18
A nesthetic technique and hip-surgery 2 0
ACS and clinical outcome 21
Etiology and pathogenesis 22
Hip-fracture and stroke 2 6
Aims of the study 2 7
Patients 28
Methods 2 9
Results
ACS frequency 32
Predisposing ACS factors 3 4
A nesthetic technique and ACS 37
ACS and clinical outcome 38
ACS diagnosis and documentation 39
In terv en tio n 41
Discussion
ACS frequency 43
Predisposing ACS factors 44
A nesthesia and ACS 45
ACS and clinical outcome 4 6
ACS diagnosis and docum entation 47
In tervention 49
Etiology and pathogenesis 51
Prevention and treatm en t 58
General summary and conclusions 5 9
Acknowledgements 61
References 63
Original papers
I 77
II 85
III 95
IV 117
V 135
VI 151
A B B R E V IA T IO N S
ACS = Acute confusional state ADL = Activities of daily living C.I. = Confidence interval CNS = Central nervous system CT = Computed tomography DEX = Dexamethasone
DSM-III = Diagnostic and statistical m anual of m ental disorders (third edition)
DSM-III-R = Diagnostic and statistical m anual of m ental disorders (third edition-revised)
DST = D exam ethasone Suppression Test GA = General anesthesia
HPA axis = H ypothalam ic-pituitary-adrenal axis IL = Interleukin
MMSE = Mini m ental state exam ination PAI = Plasminogen activator inhibitor RA = Regional anesthesia
RAS = Reticular activating system TLA = Transitory ischemic attack
A B ST R A C T
ACUTE CONFUSIONAL STATE (DELIRIUM).
Clinical studies in hip-fracture and stroke patients.
Yngve G ustafson, D epartm ents of Geriatric Medicine and Internal Medicine, Umeå University, Umeå, Sweden. D epartm ent of Geriatric Medicine, Karolinska Institute, Stockholm, Sweden.
Acute confusional state (ACS) or delirium according to DSM-III-R holds a central position in the medicine of old age. ACS is a common and som etim es the only symptom of diseases and medical complica
tions in the elderly patient.
The aim of this study was to elucidate ACS in patients with femoral neck fra c tu re s an d p a tie n ts w ith acu te stroke w ith reg ard to frequency, predictors, possible pathogenetic m echanism s, associated complications, assessm ent and docum entary routines and the clinical outcome for the patients. An intervention program to prevent p o st
operative ACS based on our results was developed and evaluated.
The m ain findings of the stu d y were high frequencies of ACS in elderly p atien ts w ith femoral neck fractures (61%) and in p atients w ith acute stroke (48%). The m ain risk factors for ACS in patien ts w ith femoral neck fractures were old age, diseases and drug tre a t
m ent interfering with cerebral cholinergic metabolism. There was no link betw een a n ae sth etic techn iq u e and ACS b u t th e connection betw een peroperative hypotension, early postoperative hypoxia and ACS was close.
In stroke p atien ts the degree of extremity paresis and old age were independent ACS risk factors. ACS was commonly associated with post stroke complications su ch as myocardial infarction, pneum onia, urinary infection and urinary retention. In stroke patients there was a close connection betw een high hypothalam ic-pituitary-adrenal axis (HPA-axis) activity and ACS. High HPA-axis activity and disturbances in th e cerebral cholinergic system m ay be two im p o rtan t ACS m echanism s.
A correct diagnosis is a prerequisite for proper tre a tm e n t of ACS and its underlying causes. In the orthopaedic w ards both physicians and n u rse s diagnosed and docum ented ACS poorly and therefore associated complications were insufficiently treated.
The intervention program for postoperative ACS, aimed m ainly at p ro te c tin g th e cereb ral oxidative m etabolism an d th e re b y the cerebral cholinergic m etabolism w hich is especially sensitive to hypoxia. Postoperative complications associated w ith ACS were also treated. The intervention resu lted in reduced frequency, d u ratio n and severity of postoperative ACS and in shorter orthopedic ward stay for p atien ts with femoral neck fractures.
Key words: Acute confusional state, delirium, elderly, stroke, femoral neck fractures, acetylcholine, cortisol.
ORIGINAL PAPERS
I. G ustafson Y, Berggren D, B rän n strö m B, B u ch t G, Norberg A, H ansson L-I, Winblad B. Acute confusional states in elderly patients tre a ted for fem oral neck fracture. J Am G eriatr Soc 36:525-530,
1988.
II. Berggren D, G ustafson Y, Eriksson B, B ucht G, H ansson L-I, Reiz S, W inblad B. Postoperative confusion in elderly p atien ts w ith femoral neck fractures. A nesth Analg, 394:497-504, 1987.
III. G ustafson Y, O lsson T, Eriksson S, A splund K, B ucht G. Acute confusional states in stroke patients. C erebrovascular Dis, accepted for publication.
IV. G ustafson Y, Olsson T, Asplund K, Hägg E. Acute confusional states (Delirium) early after stroke are associated w ith hypercortisolism . Subm itted.
V. G u stafso n Y, B rän n strö m B, Norberg A, B u ch t G, W inblad B.
U nderdiagnoses and poor docum entation of acute confusional states in elderly hip-fracture patients. Subm itted.
VI. G ustafson Y, B rännström B, Berggren D, R agnarsson J-I, Sigaard J , B ucht G, Reiz S, Norberg A, Winblad B. A geriatric-anesthesiologic program aim ed a t red u cin g acu te confusional s ta te s in elderly p a tie n ts tre a te d for fem oral n eck frac tu re s. J Am G eriatr Soc, accepted for publication.
IN T R O D U C T IO N
HISTORY
Acute confusional state (ACS) or delirium w as one of the first m ental d iso rd e rs d escrib ed in th e lite ra tu re . A bout 2 5 0 0 y e a rs ago, H ippocrates described ACS as a m ental disorder of physiologic origin in a different terminology though. Several of his observations are still relevant, for example "When a delirium or raving is ap peased by sleep, it is a good sign" and "Difficulty of breathing an d delirium in continual fevers are mortal". Greek and Roman w riters used the term phrenitis which refers to both diaphragm and mind. The soul or seat of life w as considered to be in the diaphragm and the disruption of th e u n io n betw een m ind and senses was suggested as the cause of phrenitis. This view on ACS as a disruption of the integrative system of m ental functioning is in line w ith m odern perspectives on the pathophysiology of ACS. For a review of the history of ACS see the m onograph by Lipowski (Lipowski 1990).
The lite ra tu re from the 19th cen tu ry c o n tain s excellent clinical descriptions of ACS. One of them made by Savage in 1887 proposes a m u ltifa c to ria l a p p ro a c h to ACS b e c a u s e "th ere a re sev eral predisposing cau ses which m ay have been in operation for a long time, as well as one or more exciting causes which m ay have been in action for m uch shorter periods" (Savage 1887).
TERMINOLOGY
ACS is one of th e m o st com m on a n d im p o rta n t form s of psychopathology in the elderly (Lipowski 1989). ACS is perh ap s the m ost frequent presenting symptom of disease in th e medicine of old age (Hodkinson 1976, Lipowski 1989). The stu d y of ACS h a s been plagued by term inological confusion o bstructing research , n u rsin g and m edical care, as well as com m unication and education in th e field. In Table 1 some of the synonyms of ACS used in the literature are presented. The lack of uniform terminology would have been a m inor problem if con sisten t diagnostic criteria h ad been used. The u se of DSM-III an d DSM-III-R criteria for delirium h a s m ade it possible to com pare research re su lts (APA 1980, APA 1987). For reaso n s discussed u n d e r diagnostic criteria we have chosen to use the term Acute Confusional State (ACS) in this study.
TABLE 1. »SYNONYMS1 FOR ACUTE CONFUSIONAL STATE (ACS) USED IN THE ENGLISH LITERATURE.
Acute brain dysfunction Acute brain failure Acute brain syndrome Acute cerebral insufficiency Acute cognitive disorder Acute confusion
Acute confusional insanity Acute organic b rain syndrome Acute organic psychosis Acute organic reaction Acute organic syndrome
Acute psychoorganic syndrome Agitated confusion
Agitated delirium Brain dysfunction
Cerebral insufficiency syndrome Clouded state
Confusion
Confusional state Delayed psychosis Deliria of fever Delirious state Delirium
Delirium nervosum Dysergastic reaction Em ergency delirium Encephalopathy Exogenous psychosis
Infective exhaustive psychosis Intensive care syndrome Mental confusion
Metabolic encephalopathy Organic confusion
Pharmacotoxic psychosis P hrenitis
Phrensy
Postanesthetic delirium Postoperative confusion Postoperative delirium Postoperative insanity Postoperative psychosis Pseudodem entia
Pseudosenility
Reversible cognitive dysfunction Reversible dem entia
Reversible m adness Reversible toxic psychosis Senile delirium
S tates of excitement Subacute befuddlem ent Symptomatic psychoses Toxic confusion
Toxic confusional state Toxic delirious reaction Toxic delirium
Toxic encephalopathy Toxic-infectious psychoses Toxic psychosis
T ransient behavioural syndrome T ransient cognitive disorder V ascular psychotic organic brain syndrome
DIAGNOSTIC CRITERIA
DSM-III criteria for delirium (APA 1980) are:
A. Clouding of consciousness (reduced clarity of aw areness of the environm ent), w ith reduced capacity to shift, focus an d su sta in attention as to environmental stimuli.
B. At least two of the following:
1. perceptual disturbance, m isinterpretations, illusions, or hallucinations
2. speech a t times incoherent
3. disturbance in the sleep-wakefulness cycle, w ith insom nia or day-time drow siness
4. increased or decreased psychomotor activity C. D isorientation and impaired memory (if possible to test).
D. Clinical features developing over a sh o rt period of time (usually hours or days) and tending to fluctuate during the course of a day.
E. Evidence, from the history, physical exam ination or laboratory te sts of a specific organic factor judged to be etiologically related to the disturbance.
In 1987 the DSM-III-R was published as a revision of the DSM-III.
DSM-III-R criteria for delirium (APA 1987) are:
A. Reduced ability to m ain tain atten tio n to external stim uli (e.g., q u estio n s m u st be repeated b ecau se a tte n tio n w anders) a n d to a p p ro p ria te ly sh ift a tte n tio n to new e x te rn a l stim u li (e.g., perseverates answ er to a previous question).
B. Disorganized thinking, as indicated by ram bling, irrelevant, or incoherent speech.
C. At least two of the following:
1. reduced level of consciousness, e.g., difficulty in keeping awake during examination
2. perceptual disturbances: m isinterpretations, illusions, or hallucinations
3. disturbance in sleep-wake cycle with insom nia or daytime sleepiness
4. increased or decreased psychomotor activity 5. disorientation to time, place, or person
6. impaired memory, e.g., inability to learn new material, such as the nam es of several unrelated objects after five
m inutes, or to rem em ber p ast events, such as the history of the c u rren t episode of illness
D. Clinical features developing over a sh o rt period of time (usually hours or days) and tending to fluctuate during the course of a day.
E. E ither (1) or (2):
1. evidence from the history, physical examination, or
laboratory tests of a specific organic factor (or factors) th a t can be etiologically related to the disturbance
2. in the absence of such evidence, an etiologic organic factor can be presum ed if the disturbance cannot be accounted for by a nonorganic m ental disorder, e.g., manic episode
accounting for agitation and sleep disturbance.
The DSM-III and DSM-III-R criteria for delirium are essentially the sam e. The difference is an altered h ie ra rc h y w hich m akes no difference in substance. W hen we have applied DSM-III-R criteria on p atien ts previously assessed as acutely confused according to DSM- III, no diagnosis h as been changed.
U nfortunately DSM-III and DSM-III-R criteria (E) do n o t accept psycho-social factors as etiological for delirium . However, in m ost cases of delirium , there are several co ntributing risk factors and triggering facto rs for delirium an d therefore it is difficult to d istin g u ish betw een organic and psychological m ech an ism s for delirium . A m ultifactorial ap p ro ach to delirium is n e ce ssa ry in a sse ssm e n t as well as in treatm en t. Jolley sum m arizes the basic m echanism s producing the ACS as one: "in the elderly it is u su al for m an y factors to co n trib u te a little, ra th e r th a n one factor to contribute the whole" (Jolley 1981). In m ost cases there are probably psychosocial factors acting as risk factors or contributing triggering factors. This is particularly true of patients with dem entia. Regarding ACS as a threshold phenom enon, it is obvious th a t th e dem ented p a tie n t who h a s reduced cerebral spare capacity can develop ACS from m inor strain. We have no in stru m en t to differentiate between the biochem ical d istu rb an ce in the b rain caused by psycho-social factors and those caused by organic/m etabolic factors. As the etiology of delirium in m ost cases is multifactorial we have chosen to use the term Acute Confusional State (ACS) in this study. However, the DSM- III and DSM-III-R criteria for delirium are fulfilled in all aspects in
patien ts classified as being in an acute confusional state (ACS) in all the papers.
A nother problem with the DSM-III and DSM-III-R criteria is th a t the diagnosis is sometimes technically difficult in a single given situation due to two criteria, nam ely rapid onset and fluctuating sym ptoms.
The fulfilm ent of th e se c riteria dem an d s an observ atio n of a fluctuating course or th a t relatives or caregivers can report a rapid onset and a fluctuating course. In clinical practice, w hen in doubt, it is n ecessary to make a provisional ACS diagnosis and im m ediately assess the patient for potential causes.
CLINICAL FEATURES
In ACS th e h ig h est integrative functions of th e b rain , s u c h as perception, processing and retrieval of inform ation are disorganized (Geschwind 1982). This m akes the acutely confused patient more or less incapable of thinking and acting in a rational and goal-directed m an n er (Lipowski 1990).
The essential features of ACS are the reduced ability to m aintain the attention paid to external stimuli and to appropriately shift attention to new ex tern al stim uli; th e disorganized th in k in g resu ltin g in red u ced clarity of speech th a t a p p ea rs ram bling, fragm entary, disjointed, irrelevant or incoherent. The syndrom e also includes a re d u c e d level of c o n sc io u s n e s s , se n so ry m is in te rp re ta tio n s , d istu rb a n c e s in th e sleep-w ake cycle and in creased or red uced psychom otor activity. The p atien t is usually disorientated to time, place, situ a tio n a n d /o r person. The onset is often rapid and the course fluctuates in a typical m anner and the d uration is short, a t least if the etiologic fa cto r/facto rs is /a re treated (Lipowski 1989, DSM-III, DSM-III-R).
ACS may appear in three clinical variants: 1. a hyperactive variant, characterized by psychom otor over-activity; 2. a hypoactive variant, characterized by reduced psychomotor activity and apathy; 3. a mixed v a ria n t w hich sh ifts rapidly betw een hyperactive an d hypoactive behaviour (Lipowski 1990). Many studies, old stu d ies in particular, have focused mainly on ACS with an agitated, restless and disturbing symptomatology. The hypoactive, som etim es stu p o ro u s type m ay be m isdiagnosed by the clinician and the necessary a sse ssm e n t of its cause is th u s not performed.
DIFFERENTIAL DIAGNOSIS
ACS m ay sim ulate m any types of m ental disorders in the elderly. In m ost cases the differential diagnosis concerns dem entia (Lipowski 1982). The two syndrom es often coincide which som etim es m akes a distinction betw een them difficult. ACS in a p a tie n t not assessed previously m akes it im possible to diagnose dem entia as th e ACS sym ptom s interfere with the proper assessm en t of dem entia. Both diagnoses are given only w hen there is a definite history of p re existing dem entia. In m ost cases the typical rapid onset, fluctuating course, disturbed attention and clouding of consciousness make the ACS diagnosis simple. When there is u n certain ty a provisional ACS diagnosis m u st be m ade and a consequent assessm en t of underlying d isea ses m u st be perform ed. In tim e th e p ro p er diagnosis will appear.
In some cases depression w ith cognitive im pairm ent and psychotic sym ptom s m ay also cau se diagnostic problem s. S chizophrenia, schizophreniform disorders and other acute psychoses m ay appear w ith hallucinations, delusions and disordered thinking (Daniel 1985).
In an elderly p atien t w ith cognitive im pairm ent due to pre-existing d iseases these diagnoses can cause diagnostic problem s. Table 2 presen ts the typical symptoms of the syndromes or diseases th a t can cause diagnostic problems, constructed and modified after the DSM- III-R (APA 1987) and th e m onograph m ade by Lipowski (Lipowski 1990).
TABLE 2. A SIMPLIFIED GUIDE TO THE TYPICAL CLINICAL FEATURES OF ACS, DEMENTIA, DEPRESSION AND ACUTE FUNCTIONAL PSYCHOSIS.
FEATURE ACS DEMENTIA DEPRES
SION
ACUTE FUNCTIONAI PSYCHOSIS
Age at initial >60 >60 All ages <40 onset
Onset Minutes- Months Weeks Days-
hours Weeks
Course Fluctuating Stable Fluctuating Stable
Duration Hours- Months- Weeks- Weeks-
weeks years m onths m onths
Consciousness Reduced Clear Clear Clear
Em otions Fear, agony Indifferent Discomfort Various depending upon type
Awareness Fluctuating Normal Normal May be
disordered
Alertness Fluctuating Normal Usually U sually
norm al norm al
A ttention Globally Usually Usually U sually
disordered norm al norm al norm al
Cognition Globally Globally Normal or U sually
disordered impaired fluctuating norm al
Orientation Impaired Impaired Usually U sually
fluctuates norm al norm al
Memory Impaired Impaired May be May be
impaired impaired
T hinking Disorga Impaired Normal Often
nized abstraction disordered
Perception Distorted Often Normal Som etim es
norm al disturbed
H allucinations Visual and/ Absent Absent Predom inantly
or auditory auditory
Delusions Fleeting un Absent Absent Sustained and
systematized systematized
Psychom otor Increased Normal Normal or Varies depending
activity decreased slightly on type of
shifting decreased psychosis
Speech Incoherent Dysphasia Normal Normal,
slow or rapid Sleep-Wake Disturbed Normal or Som etim es Som etim es
cycle often fragmentary disturbed disturbed
reversed
Involuntary Asterixis or Often Absent U sually
m ovem ents tremor absent absent
com m on
Physical illness Present Usually Usually Absent
absent absent
Drug toxicity Often Absent Absent Absent
present
Awareness of Unaware Unaware or Highlights U sually
symptoms conceals disabilities unaware
Answers Wrong "Near miss" I don't U sually and conceals know correct
EEG Abnorm al Normal in Normal U sually
early phase norm al
ACS FREQUENCY
Different diagnostic ACS criteria and various p atien t populations in clinical studies have resulted in incidence and prevalence rates from 0.7 - 80% (Liston 1982. MacDonald 1989, Lipowski 1990). In older studies of cognitive im pairm ent in the elderly, few au th o rs have made any distin ctio n betw een dem entia and ACS. Even fewer a u th o rs describe ACS in patients w ith dementia. The resu lts of recent studies on the frequency of ACS in different p atien t groups are sum m arized in Table 3.
TABLE 3. FREQUENCY OF ACS IN RECENT STUDIES ON ELDERLY PATIENTS.
POPULATION
S ettin g Age Pat.
(N)
ACS (%)
Author Year
General hospital General
>60 99 56 Chisholm 1982
m ed icine General
>70 173 3 0 G illick 1982
hospital General
>65 28 2 21 Erkinjuntti 19 8 7
m ed icine Medical in
All ages
133 15 Thomas 19 8 8
tensive care Nonintensive
>60 71 38* Foreman 1 9 8 9
medical care G eneral
>65 8 0 30 Rockwood 198 9
hospital >75 146 40 Bucht 19 9 0
N ursing home >75 2 03 65 Bucht 19 9 0
Home for
the aged >75 196 25 Bucht 1 9 9 0
Home care >75 172 2 5 Bucht 1 9 9 0
G eneral
m edicine >70 23 5 20* Johnson 199 0
General
m edicine >70 22 9 22* Francis 199 0
* Patients w ith dem entia excluded
** ACS diagnosed according to DSM-III or DSM-III-R criteria
POSTOPERATIVE ACS
Postoperative or p o stan esth etic confusion h a s been given a lot of interest in the literature. As early as in 1887 George Savage carefully described 'postoperative insanity' based on h is clinical experience and proposed possible etiologies (Savage 1887). A farsighted review of post-operative psychoses, risk factors and organic features su ch as 'endocrine upsets, changes in chem istry and nutritional disturbances' was w ritten in 1938 by Milton Abeles (Abeles 1938).
Postoperative confusion h as been reported to occur after different types of surgery su ch as cataract surgery (Summers 1979, Burrows 1985), prostatectom y (Ghoneim 1988), hip-fracture surgery (Morse 1771, W illiam s 1979), pelvic floor re p a ir (C hung 1987) a n d cardiovascular surgery (Morse 1969, Morse 1971). For review on postoperative confusion see W hitaker 1989. In Table 4 the frequency of postoperative ACS in recent studies are sum m arized.
Postanesthetic confusion h a s been associated with different types of prem edication a n d /o r anesthetic agents su ch as alcohol, belladonna, fentanyl and halothane (Savage 1887, Simpson 1976).
TABLE 4. FREQUENCY OF POSTOPERATIVE ACS IN RECENT STUDIES P atient
sam ple
Age Pat.
(N)
ACS (%)
Author Year
Elective hipsurgery All ages
6 0 12* Hole 1980
General surgery >65 100 14 M illar 1981
H ip-fracture >60 170 52* W illiam s 1985a
H ip-fracture (Intervention)
>60 5 7 44* Williams 1985b
General surgery All ages
92 42* Dieckelmann 1989
Elective orthopaedic
surgery >60 4 6 26* Rogers 1989*
H ip-fracture >60 35 4 3 Brännström 1989*
H ip-fracture
(6 m onths survivors)
>65 5 3 6 2 3 Magaziner 1990
* Patients with dem entia excluded
** ACS diagnosed according to DSM-III or DSM-III-R criteria
ACS IN STROKE PATIENTS
ACS in stroke p atien ts h a s never been studied prospectively in a re p re se n ta tiv e sam p le of stro k e p a tie n ts . T here are a few retrospective studies (de Reuck 1982, D unne 1986), several studies on selected p a tie n ts w ith different types and localisation of th eir stro k es (Mullaly 1982, Schm idley 1984, Mori 1987, Garcia-Albea
1989) and several case rep orts (H orenstein 1967, M edina 1974, M esulam 1976, M edina 1977, Levine 1982, Graff-Radford 1984, S a n ta m a ria 1984, Price 1985, B alter 1986, B ogousslavsky 1988, Devinsky 1988). It is difficult to apply DSM-III or DSM-III-R criteria on retrospective study sam ples and a retrospective approach is likely to lead to an un d erestim atio n of ACS. In one retrospective study, using DSM-III criteria for ACS, 150 of the 450 (33%) p atien ts with c e re b ra l in fa rc tio n s w ere d is o rie n ta te d or ”confused" u p o n p resen tatio n , and 112 of the 211 (53%) w ith sp o n tan eo u s b rain hem orrhage were diso rien tated or "confused” (Dunne 1986). In a study of patients with right middle cerebral artery infarction, 25 out of 41 (61%) were judged to be acutely confused (Mori 1987). ACS h a s b een rep o rted to be more com mon in p a tie n ts w ith right h em isphere lesions th a n in p a tie n ts w ith left hem isp h ere b rain lesions (Dunne 1986). In different case rep o rts, ACS h a s been associated w ith cerebrovascular lesions affecting a large variety of specific locations su ch as right middle cerebral artery infarctions, left posterior infarctions, medial tem poro-occipital infarction, after infarctions of the hippocam pal region, the fusiform and lingual gyri or in the th alam u s (Horenstein 1967, Medina 1974, Medina 1977, M esulam 1976, M ullally 1982, de R euck 1982, Levine 1982, Schmidley 1984, Graff-Radford 1984, Santam aria 1984, Price 1985, D unne 1986, Mori 1987, B ogousslavsky 1988, D evinsky 1988, Garcia-Albea 1989). ACS h as also been described in p atien ts with m ultiple sm all cerebral in farctio n s (Balter 1986). However, the definition of ACS differs betw een vario u s stu d ies, an d only one retrospective study used the DSM-III criteria (Dunne 1986).
PREDISPOSING ACS FACTORS
A m u ltifac to rial ap p ro a ch co n sid erin g th e p a tie n t's p revious diagnoses, medication and psycho-social capacity is necessary in the a s s e ss m e n t of ACS (Arie 1981). There are often one or more
preventable or treatable risk factors or triggering factors in elderly p atien ts (Jolley 1981, Lipowski 1990).
The literature contains an overwhelming num ber of case reports b u t few sy stem atic an aly ses of risk factors and p o tential triggering m echanism s for ACS.
The following is a sum m ary of factors reported to increase the risk for ACS:
Age: Im portant ACS risk factor according to m ost stu d ies. (Morse 1969a, Morse 1969b, Morse 1971, Hodkinson 1973, V arsam is 1978, Liston 1982, Williams 1985b, Dickelmann 1989, Lipowski 1990).
Gender: Most stu d ies report a sim ilar ACS frequency in m en and women (Judge 1977, Lipowski 1990). However, in th ree stu d ie s a higher ACS frequency h as been reported among m en (Simon 1963, Kay 1972, Seymour 1983).
Dem entia: Progressive degenerative b rain diseases lower th e ACS th re s h o ld by red u c in g th e n e u ro tra n s m itte r m etab o lism , e.g.
acetylcholine (Gottfries 1983, G ottfries 1987). It is easy for a dem ented p a tie n t to becom e acutely confused due to biological, psychological or environm ental factors (Morse 1969a, Morse 1969b, H odkinson 1973, V arsam is 1978, B eresin 1988, H ege-Scheuing 1989, Lipowski 1990, F rancis 1990, Jo h n so n 1990b, T h ien h au s 1990).
Previous stroke: Stroke h as also been reported to be a predisposing and triggering factor for ACS (Flint 1956, Lipowski 1990).
C ardiac disease: Several cardiac diseases are reported to predispose to ACS (Wolff 1935, F lint 1956, M orse 1969a, M orse 1969b, V arsam is 1978).
D epression increases the p a tie n t's vulnerability (Gold 1988a, Gold 1988b) and increases the risk for ACS (Wolff 1935, Morse 1969a, M orse 1969b, V arsam is 1978). O ther preoperative psychological s ta te s , e.g. an x iety , h a s also b een re p o rte d to p re d ic t th e postoperative psychological course (Abraham 1961, V arsam is 1978).
Impaired hearing is an im portant ACS risk factor according to several studies (Hodkinson 1973, Ju d ge 1977).
Im paired vision h a s also been reported to be a n ACS risk factor (Hodkinson 1973, Ju d g e 1977, Lipowski 1990).
Drugs: T reatm ent with m any different groups of drugs, drugs with anticholinergic effects in particular, h a s been reported to increase
the ACS risk or to trigger ACS in the elderly (Itil 1966, Tune 1981, Liston 1982, Ju d g e 1977, Judge 1987, Gordon 1988, Miller 1988, Forem an 1989a, Hege-Scheuing 1989, Francis 1990) and especially in the elderly w ith dem entia diseases (Thienhaus 1990).
ANESTHETIC TECHNIQUE AND HIP-SURGERY
The incidence of hip-fracture is rapidly increasing in all the w estern world (Jensen 1980b, Nickens 1983). Old age is an im portant risk factor for hip fractures b u t explains only a m inor p a rt of the increase (Zetterberg 1982). A n esth esists would like to select an an esthetic technique resulting in m inim al postoperative m orbidity for th e old and vulnerable p atien t w ith a fracture of the femoral neck (Covert 1989). General anesthesia is reported, in older studies, to cause more com plications in elderly patien ts th a n regional a n esth esia (McLaren 1978). A general opinion in th e lite ra tu re before 1980 w as th a t general a n e s th e sia w as com plicated w ith m ore adverse cerebral effects th a n regional a n esth e sia (G authier 1963). G authier on the o th er h a n d reported a sim ilar m orbidity an d m ortality rate after spinal anesthesia and general anesthesia. In Table 5 some randomized studies on hip surgery are sum m arized. Neither general nor regional a n e s th e sia are convincingly su p p o rted by th e re s u lts regarding m ortality or postoperative cognitive functioning.
TABLE 5. GENERAL ANESTHESIA (GA) VERSUS REGIONAL ANESTHESIA (RA).
P atient sam ple
N GA or RA better for postop cognition
Difference Author in m ortality
Year
H ip-fracture 55 - GA>RA McLaren 1978
H ip-replacem . 60 RA better th a n GA No Hole 1980
H ip-fracture 100 - No McKenzie 1980
H ip-fracture 60 - No White 1980
H ip-fracture 132 - No Davis 1981
H ip-fracture 169 - No Wikström 1982
H ip-replacem . 30 GA=RA No Riis 1983
H ip-fracture 150 - GA>RA McKenzie 1984
H ip-fracture 40 GA=RA No Bigler 1985
H ip-fracture 57 8 - No V alentin 1986
H ip-fracture 53 8 - No D avis 1987
H ip-replacem . Prostatectom y H ysterectom y
105 GA=RA No Ghoneim 1988
Hip or knee
replacem . 146 GA=RA No Jones 1990
- = not assesed
ACS AND CLINICAL OUTCOME
The m ortality rate for patients developing ACS h as been reported to be higher com pared w ith th a t of p atien ts who do n o t develop ACS (Bedford 1959, Roth 1959, Simon 1963, Rabins 1982, Liston 1982, W eddington 1982, Trzepacz 1985, Rockwood 1990, F rancis 1990).
ACS is probably underestim ated as a risk factor contributing to death in m any groups of patients (Weddington 1982).
In several studies prolonged w ard-stay h a s been reported for p atien ts w ho develop ACS (Glass 1977, S h ep p eard 1980, L am ont 1983, T hom as 1988, Levkoff 1988, B rän n strö m 1989, Rockwood 1990, B rännström 1991). The prolonged w ard-stay is often associated with
m any complications which eure caused at least partly by the ACS. ACS h a s also been reported to be associated w ith poorer rehabilitation re su lt (Magaziner 1990). The acutely confused p atien t is reported to be a t the risk of being hospitalized as staff do not expect him to be able to m anage on h is own. This could co n trib u te to prolonged dependency u p o n caregivers also after the ACS h a s been reversed (B rännström 1991). It h a s been shown th a t elderly p a tie n ts' m ental im pairm ent influences the n u rse -p atien t in teractio n negatively. In confused patients the psychosocial interaction w as particularly poor and the physical care w as given priority (Armstrong-Esther 1986).
ACS patients have difficulties in cooperating w ith staff as they do not u n d e rstan d nor rem em ber instructions. They often exhibit behaviour disturbances a n d /o r act perilously dem anding continuous supervision.
The ACS-associated com plications need to be attended to and often an acutely confused p atien t is probably incapable of experiencing th irst or h unger and even more incapable of satisfying these needs (B rännström 1989).
ETIOLOGY AND PATHOGENESIS
T here are two m ajor h y p o th e se s a b o u t th e p a th o g en e sis and path ophysiology of ACS (Lipowski 1987). The first h y p o th esis su g g ests th a t a red u ctio n in th e cerebral m etabolism an d the consequent reduction in n euro tran sm itters, especially acetylcholine, co n trib u tes to th e developm ent of ACS (Blass 1979, B lass 1983).
This hypothesis is supported by stu d ies showing th a t the cerebral acetylcholine sy n th e sis is especially sen sitiv e to hypoxia an d hypoglycemia (Gibson 1981, Hirsch 1984). A close link between ACS and anticholinergic activity h a s been reported by several au th o rs (ltd 1966, Tune 1981, Mondimore 1983, Miller 1988, T hienhaus 1990).
ACS caused by anticholinergic m edication can be reversed by m eans of p h y so stig m in e, a c h o lin e e s te ra s e in h ib ito r (G reen 1971, A quilonius 1978). The second hypothesis suggests th a t ACS is a reaction to stress m ediated by elevated plasm a cortisol and its effects on th e b ra in (Kraal 1962, Kraal 1975, C arp en ter 1982, McEwen 1987, McEwen 1988). High cortisol levels have been suggested to affect the n euro n function of the central nervous system (Sapolsky 1985, de Kloet 1987) and the cognitive function as a re su lt of this (Micco 1980, Reus 1987, Issa 1990, Wolkowitz 1990). This m ay be
m o st p ro n o u n ced in th e h ip p o cam p u s, w here th e n u m b e r of glucocorticoid receptors is particularly high and th u s comprom ising th e cognitive fu n ctio n (Micco 1980, G ilad 1987, Jo e ls 1989, A rm a n in i 1990, S ap o lsk y 1990a). G lu co co rtico id s e n d a n g e r hippocam pal neurons probably by impairing their energy m etabolism (Sapolsky 1986a). This is why glucocorticoids probably increase the n e u ro n a l vu ln erab ility to hypoxia, isch em ia and hypoglycem ia.
S u pplem enting w ith 'b rain fuels' in anim al m odels red u ces th e toxicity of glucocorticoids in the hippocam pus (Sapolsky 1986a). It h a s also been reported th a t cortisol m odulates cholinergic receptors in the subcortical limbic forebrain (von Euler 1990).
In several studies, ACS h a s been found to occur after hippocam pal stro k e (M edina 1974, G raff-Radford 1984, S a n ta m a ria 1984, Bogousslavsky 1988).
Acetylcholine is a n im portant direct and indirect HPA-axis regulator (Gilad 1987, Calogero 1988). A close connection betw een stre ss, h ip p o c a m p a l c h o lin e rg ic s y ste m , co g n itiv e f u n c tio n a n d glucocorticoids h a s been d em o n strated in anim al m odels (Gilad 1987, Lai 1990). High cortisol levels have been rep o rted to be associated w ith postoperative ACS 2-4 days after elective surgery (McIntosh 1985).
In m ost cases of ACS one or both of these m echanism s are involved in th e developm ent of th e cognitive d istu rb an ces. O ther m echanism s interfering w ith cerebral m etabolism and tra n sm itte r activity may also be of im portance such as the factors interfering w ith glutam ate m etabolism (Sapolsky 1990a). Protection of the cerebral oxidative m etabolism and a reduction in stress m ediated by high cortisol levels th u s seem to be the m ost im portant possibilities in ACS prevention and treatm ent.
In Table 6, some suggested a n d /o r docum ented etiological factors are presented, stru ctu red according to the two m ain hypotheses of ACS pathophysiology. Psycho-social factors, which have been suggested to co n tribu te to or cause ACS, could act through the stress-cortisol system. Some psycho-social factors, which have been suggested to be risk factors a n d /o r ACS triggering factors are presented in Table 6 u n d er II B.
TABLE 6 . SUGGESTED AND/OR DOCUMENTED ACS CAUSES IN THE LITERATURE. THE ACS CAUSES ARE STRUCTURED ACCORDING TO THE TWO MAIN HYPOTHESES OF ACS PATHOPHYSIOLOGY.
I. ACS MEDIATED MAINLY BY DISTURBANCES IN THE CHOLINERGIC FUNCTION OF THE BRAIN. (The acetylcholine synthesis is especially sensitive to disturbances in the brain energy metabolism, e.g. hypoxia, hypoglycemia. Disturbances in the cholinergic system is closely associated with cognitive disturbances).
A. DISTURBED CEREBRAL OXYGENATION
1. Pulmonary diseases, e.g. pneumonia, pulmonary embolism
2. Cardiac diseases, e.g. congestive heart diseases, pulmonary oedema, cardiac arrhythmia, myocardial infarction
3. Anaemia
4. Hypoperfusion, e.g. peroperative hypotension, hypovolemia (bleeding, dehydration), ortostatism, aortic stenosis, ischemic brain disease, vasculitis, hyperventilation syndrome, disseminated
intravascular coagulation, increased blood viscosity (e.g. polycyternia) 5. Carbon monoxide poisoning
6. Methemoglobinemia
B. DEPRIVATION OF ENERGY OR NUTRITIVE SUBSTANCES
1. Hypoglycemia, e.g. insulin-coma, spontaneous (i.e.insulinoma, liver disease, starvation, cortisol deficiency), drug-induced (i.e.oral
antidiabetics, haloperidol)
2. Cofactor deficiency, e.g. thiamine, niacine, pyridoxine, vitamin B12, vitamin E, vitamin C, folate
3. Hypoproteinemi
C. TOXIC DISTURBANCES IN THE CHOLINERGIC SYSTEM
1. Drugs, e.g. neuroleptics, tricyclic antidepressants, cortisone, antihistamines, other drugs with anticholinergic effects
II. ACS AS A REACTION TO STRESS PROBABLY MEDIATED MAINLY BY HYPERCORTISOLISM. (Cholinergic neurons in hippocam pus might be especially sensitive to hypercortisolism and glucocorticoids endanger hippocampal neurons by impairing their energy metabolism. Glucocorticoids probably thereby increase the damage to cholinergic neurons in the hippocampus induced by hypoxia or ischemia for instance).
A. ORGANIC FACTORS
1. Trauma, e.g. fractures, bum s, contusions
2. Acute medical diseases, e.g. myocardial infarctions, congestive heart failure, acute stroke, deep vein thrombosis, pulmonary embolism 3. Acute surgical diseases, e.g. pancreatitis, cholecystitis, gastric ulcer 4. D iseases with hypercortisolism, e.g. Cushing's syndrome
5. Urinary retention 6. Allergic reactions 7. Fecal impaction
B. TREATMENT WITH CORTICOSTEROIDS C. PSYCHOSOCIAL FACTORS
1. Severe emotional stress, e.g. fatigue, pain, grief, anxiety, relocation 2. Secondary to psychiatric disorders, e.g. depression, mania, cycloid psychoses
3. Immobilization
4. Sensory deprivation, e.g. blindness, deafness 5. Sensory overload e.g. noise
6. Sleep deprivation
III. OTHER METABOLIC OR TOXIC ACS-MECHANISMS DISTURBING THE BRAIN METABOLISM IN A MORE GENERAL WAY (Causes probably partly acting through previous m echanism s, hypoxia, hypoperfusion a n d /or otherwise disturbed transm itter m etabolism partly caused by stressm ediated hypercortisolism ).
A. FEBRILE STATES 1. Urinary infections 2. Pneumonia 3. Septical infections B. HYPOTHERMIA
C. ENDOCRINE DISORDERS 1. Pituitary disorders 2. Hyper/hypothyreoidism 3. Hyper/hypoparathyreoidism 4. Addison's disease
5. Pheochromocytoma
D. WATER AND ELECTROLYTE DISTURBANCES
Different osmolality and electrolyte disturbances can cause ACS, e.g.
hypo-osmolality (water intoxication), hyper-osmolality (nonketotic diabetic coma), hypo- and hypercalcemia, hypo- and hyperkalemia hypo- and hypernatremia, hypo- and hypermagnesemia, hypo- and hyperchloremia, hypo- and hyperphosphatemia
E. ACID-BASE DISTURBANCES 1. Alkalosis/Acidosis F. KIDNEY DISEASES
1. Uraemia G. LIVER DISEASES
1. Liver precoma 2. Porphyria H. DRUGS
Most drugs in toxic or therapeutic doses can cause ACS, e.g. penicillin, anticonvulsants, cardiac glycosides, sedative drugs, salicylates, analgetics, 1-dopa, amantadine, selegiline, bromokriptine, Cimetidine, timolol, anti tumour agents, barbiturates
I. ALCOHOL
1. Intoxication 2. Withdrawal J. POISONS
Different poisons can cause ACS, e.g. paraldehyd, methyl alchohol, ethylene glycol, heavy metals, cyanide, bromid, insecticides
IV. OTHER CENTRAL NERVOUS DISORDERS (Causes probably partly acting through previous m echanism s, hypoxia, hypoperfusion an d /or otherwise disturbed transmitter metabolism partly caused by stressmediated hypercortisolism).
A. HEAD TRAUMA 1. Concussion
2. Subdural hematoma B. EPILEPSY
1. Post-ictal state 2. Seizure disorders C. INFECTIONS
Most cerebral infections can cause ACS, e.g. meningitis, encephalitis, neurosyphilis, borreliosis, cerebral abscess, toxoplasmosis, malaria D. BRAIN TUMOURS
E. MULTIPLE SCLEROSIS
HIP-FRACTURE AND STROKE
Hip fractu res and stroke cause a great deal of suffering for m any elderly people and are quan titativ ely im p o rtan t d iseases in th e elderly in th e w estern world (Ceder 1979, J e n s e n 1980a J e n s e n 1980b, Je n se n 1980c, Luthje 1982, Goldstein 1983, Nickens 1983, Wallace 1983, W hishnant 1984, Eriksson 1987).
Fem oral neck fractu res predom inantly strik e th e old wom an. As m entioned previously th e incidence of hip fra c tu re s is rapidly increasing in all the w estern world (Zetterberg 1982, J e n se n 1980b, Je n se n 1980c, Nickens 1983, Falch 1985). In four of the papers ACS was studied in patients operated on for femoral neck fractures which is one of th e m ost common op eration s am ong old people. The o p eratio n is u su ally rap id , an d stan d a rd iz e d and peroperative bleeding is rare. When studying the postoperative consequences of a n esth e tic technique it is im p o rtan t th a t th e surgical procedure rem ains relatively constant.
In the United States alone there are 1.7 million stroke survivors at any given time (Grotta 1988). Patients w ith stroke are increasing in n u m b er in Sweden and rep resen t the p atien t group consum ing the highest percentage of hospital care (MFR 1986). Stroke patien ts like hip fracture patien ts have a high m ean age b u t stroke is som ew hat more common among men. The organisation of stroke care into non- in ten siv e stro k e u n its h a s improved th e care and th ereb y the prognosis for stroke p a tie n ts (Strand 1985, E riksson 1987). The stroke u n it in Medical D epartm ent 1 in Umeå w as opened in 1978 and h a s been proved to be a good b asis for research and for the development of stroke care (Strand 1985, Eriksson 1987).
AIMS OF THE STUDY
The aim s of this study were:
- the elucidation of ACS in patien ts with femoral neck fractures and p a tie n ts w ith acu te stroke w ith regard to frequency, predictors, p o ssib le p a th o g e n e tic m e c h a n ism s, a sso c ia te d co m p licatio n s, assessm en ts and docum entary routines and the clinical outcome for the patients.
- th e developm ent an d evaluation of a n intervention program to prevent an d tre a t ACS in p a tie n ts operated on for fem oral neck fractures.
P A T IE N T S
Paper I: O nehundred and eleven consecutive patients 65 years old or older, w ith fem oral neck frac tu re s adm itted to the O rthopaedic d ep artm en t of Umeå University Hospital betw een M arch 1983 and J u n e 1984.
Paper II: Fifty-seven p atien ts, lucid a t adm ission, 65 years old or older, w ith femoral neck fractu res, th a t could be random ized to receive eith er general or regional a n e sth e sia an d adm itted to the O rthopaedic departm ent of Umeå University Hospital between M arch 1983 and November 1984. Forty-five of the fifty-seven patien ts were also included in Paper I.
Paper III: O nehundred and forty-five consecutive stroke patients of all ages adm itted to th e stroke u n it of the d ep artm en t of In tern al M edicine of Umeå U niversity H ospital betw een April 1983 an d December 1984.
P aper IV: E ighty-three selected stro k e p a tie n ts of all ages w ith su p ra ten to rial ischem ic stroke adm itted to the stroke u n it of the d e p a rtm e n t of In te rn a l M edicine of Um eå U niversity H ospital between J u n e 1983 and March 1986.
Paper V: All p a tie n ts in Papers I (N = lll) and II (N=57) an d two retrospective p atien t sam ples com parable w ith th a t of Paper I. The first retrospective control sample included: all patien ts 65 years old or older, irrespective of p refracture m ental state, adm itted to the O rthopaedic d ep artm en t of Umeå University H ospital during 1980 (N=66). The second retrospective control sam ple, w ith th e sam e inclusion criteria was adm itted to the departm ent of General Surgery of Piteå County Hospital during 1980 and 1981 (N=68).
Paper VI: O nehundred and three consecutive patients, 65 years old or older, w ith femoral neck fractures adm itted to the O rthopaedic d ep artm en t of Umeå U niversity Hospital betw een D ecember 1986 and Jan u ary 1988.
M ETH O DS
ACS w as diagnosed according to the DSM-III or DSM-III-R criteria for delirium (APA 1980, APA 1987), after clinical a ss e ss m e n ts in clu d in g : 1. P re -fra c tu re /p re -s tro k e h isto ry checked th ro u g h m edical records an d by m ean s of interview s w ith th e p a tie n ts ' families or care-givers. 2. Behaviour on the w ard assessed by direct p atien t observations an d interviews w ith th e staff. 3. O rientation, s u s p ic io u s n e s s , em o tion s, d e p re ssio n , speech , d e lu sio n s a n d hallucinations, recognition, motor function, sociability and changes in the p atien ts' m ental function assessed and registered by m eans of the Organic Brain Syndrome Scale (Gustafson 1985, Hallberg 1989). 4. A Mini-Mental State Exam ination (MMSE) w as m ade on adm ission and th en once a week during the hospital stay for all patients included in the studies on stroke patients (Folstein 1975). MMSE was performed when considered necessaiy for the ACS diagnosis in the patients with femoral neck fractures.
All p atien ts in th is stu d y were observed several tim es per day and assessm en ts including tests and interviews were carried out on the first day of adm ission and th en a t several tim es during the p a tie n ts' hospital stay. All tests, interviews w ith p atients, relatives and staff were carried out by the same physician (YG) in the studies on stroke patien ts and by three different raters in the studies on patients with femoral neck fractu res. Before the s ta rt of the stu d ie s th e th ree ra te rs assessed ten p atien ts to te st the in te rra te r reliability of the registration of the items included in the OBS-scale. The tests of these ratin g s were analyzed, and the agreem ent betw een th e ra te rs was above 90% in all ratings. While these studies were performed two of th e ra te rs collaborated in two other stu d ie s (B rännström 1989, B rän n strö m 1991) u sin g the sam e a sse ssm e n t ro u tin es. In bo th stu d ies th e agreem ent on the ACS diagnosis according to DSM-III, w as above 95% between them.
In P aper I, all p a tie n ts 65 y ears old or older, irresp ective of prefracture m ental state, operated on for femoral neck fractures with various anesthetic techniques, were studied regarding ACS frequency.
In Paper II, patien ts lucid on adm ission were random ized to receive either general or regional anesthesia.
In Paper III the sam e m ethods, as in Paper I were u sed for stroke patients.
In P aper IV a selected sam ple of p a tie n ts w ith s u p ra te n to ria l ischem ic stroke w as assessed with the dexam ethasone su pp ressio n test (DST) and compared with a healthy control population.
In Paper V d ata from the review of medical records were compared w ith clinical stu dies from the care occasions, presented in Papers I an d II. To find o u t w h e th er th e on-going clinical s tu d ie s had influenced the ph ysicians' and n u rs e s ' ACS docum entation in their case -n o te s, two o th e r retro sp ectiv e c ase-n o te sam p les on th e corresponding patient groups were studied.
The m edical records were studied in order to find the noted ACS frequency and treatm ent, notes on its consequences and the nursing activities associated w ith these notes. In the stu d y of the m edical reco rd s, ACS crite ria were explicit sta te m e n ts on ACS a n d /o r docum ented sym ptom s or behaviour indicating ACS. The analysis of th e re c o rd s a n d th e c la ssific a tio n of p a tie n ts w ere m ade independently by two of the au th o rs of Paper V (BB, YG). There was 89% exact agreem ent betw een the au th o rs regarding the diagnoses m ade from the case-note analyses. Every case of disagreem ent was subject to diagnostic discussions ending up in full agreem ent on the ACS and the dem entia diagnoses.
The intervention program (Paper VI), was based on the resu lts of our previous s tu d ie s (Papers I an d II). The in terv en tio n aim ed a t preventing postoperative ACS by protecting th e p a tie n ts cerebral oxidative m etabolism w hich w as achieved by th e prevention of hypoxia and hypoten sio n /h y p o -p erfu sio n . P atien ts who developed p o sto p erativ e ACS w ere a ss e ss e d an d tre a te d for a sso c ia te d com plications. The intervention stu d y could not be perform ed as a random ized stu d y since the re su lts of o u r previous stu d ie s h ad initiated changes in the treatm en t routines for these patients. It was also regarded as unethical, considering our previous results, not to prevent severe hypoxemia and peroperative hypotension. The resu lts of the intervention were therefore compared with the outcome of the patients in Paper I.
STATISTICS
The Systat™ statistical package was used for calculations (Wilkinson 1987, W ilkinson 1990). The chi-square test, Y ates' corrected chi- sq u a re te s t. S tu d e n t's t-te s t, M ann W hitney U -test, P earso n correlation coefficients, the odds ratios and 95% confidence intervals for odds ratios were used w hen relevant as indicated in th e text (Feinstein 1985, Sandercock 1989). The Bonferroni correction was u sed to a d ju st for probabilities. To find in d ependent clinical ACS predictors, multiple linear regression analyses were used in Papers I, II and III (Draper 1966). In the multiple linear regression models the F-ratio an d the P-value were u sed to d em o n strate th e statistic a l significance of th e model. The sq u ared m ultiple R w as u sed to illustrate the explanatory degree of the model. The predictors of the geriatric stroke rehabilitation in Paper III were calculated by the u se of orthogonal scores from a factor analysis rep resen tin g clinical variables. In Paper IV a logistic regression model (Dobson 1982) was u sed in th e SAS program package. Also in P aper VI logistic regression models were used to find independent ACS predictors in the two p atien t sam ples b u t the calculations were made in the SPSS program package. In th is th esis logistic regression m odels are also presented for the prediction models presented in Paper I and III. A logistic regression model is preferable as a multiple linear regression model may have some unw anted properties su ch as the risk of the predictions of new observations ending up outside the range [0,1]. An iterative m axim um likelihood procedure w as used in the SAS and SPSS program packages where the resu lts obtained are interpreted from the exact distribution (binomial) of the response variable (ACS).
The choice of different program packages for the logistic regression analyses w as made for technical and financial reasons. A P-value of less th a n 0.05 was regarded as statistically significant.
R E SU L T S
ACS FREQUENCY
A sum m ary of the ACS frequency in different papers are presented in Tables 7 and 8.
TABLE 7. ACS FREQUENCY IN THE STUDIED SAMPLES OF PATIENTS WITH FEMORAL NECK FRACTURES.
Paper N Mean Age
(range)
M ale/
Female
Dem entia (%)
ACS (%)
ACS>
days I. All
p atien ts n . Patients
111 79
(65-96)
2 8 /8 3 15 61 40
lucid a t adm ission V.
R etrospect.
57 78
(65-95)
1 1 /4 6 0 44 28
of paper I R etrospect.
111 79
(65-96)
2 8 /8 3 43
of paper II R etrospect.
57 78
(65-95)
1 1 /4 6 32
control 1 R etrospect.
66 79
(65-96)
2 2 /4 4 44
control 2 VI. In te r
68 78
(66-95)
2 4 /4 4 47
vention all patients Patients
103 80
(65-102)
2 8 /7 5 22 48 29
lucid a t adm ission
66 78
(65-94)
1 4 /5 2 0 27 9
- = Not assessed
TABLE 8 . ACS FREQUENCY IN THE STUDIED SAMPLES OF STROKE PATIENTS.
Paper N Mean Age M ale/ D em entia ACS ACS>7
(range) Female (%) (%) days(%)
m . Ail stro k e p atien ts
145 73 9 0 /5 5
(40-101)
6 4 8 31
IV. Selected stro k e p atien ts
8 3 75
(44-89)
5 2 /3 1 42
ACS w as common both in the representative prospective sam ple of p a tie n ts w ith femoral neck fractu res (61%) and in th a t of stroke patien ts (48%). The majority of patients developing ACS in these two sam ples were acutely confused for more th a n one week. The ACS frequency of the intervention stu d y (VI) w as lower th a n th a t of th e control stu d y (I) (61% vs 48%, p<0.05). W hen com paring p atien ts lucid a t adm ission in Paper VI w ith the corresponding p atien t sam ple in Paper II, there were fewer patien ts in the intervention stu d y who w ere acu te ly co nfused for m ore th a n seven days (9% in th e intervention study compared w ith 28% in the control study, pcO.Ol).
