Non-pulmonary Critical Care: Managing Multisystem Critical Illness Care of the critically ill patient is truly multi-system management of highly complex patients who typically have numer
Trang 1Non-pulmonary Critical Care: Managing Multisystem Critical Illness
Care of the critically ill patient is truly
multi-system management of highly complex patients who
typically have numerous acute physiological
derange-ments superimposed upon underlying medical ailderange-ments
Historically, the majority of patients admitted to
inten-sive care units (particularly medical ICUs) have
respira-tory failure requiring mechanical ventilation, often along
with other acute and chronic pulmonary problems
Much ICU-related research and education has similarly
focused on pulmonary issues such as the acute respiratory
distress syndrome (ARDS), pneumonia, and mechanical
ventilation Additionally, a great majority of intensivists
have received training in pulmonary and critical care
medicine Thus it is not surprising that the phrase
‘‘non-pulmonary critical care’’ has arisen to address many
general critical care issues However, this vast body of
knowledge might more appropriately be considered
‘‘multisystem critical care’’ as an inclusive term that
encompasses the many important organ system
derange-ments that plague our ICU patients
This issue of Seminars provides scholarly and
clinically relevant reviews of major non–pulmonary
or-gan dysfunction in the ICU setting Clearly, a compre-hensive review of the numerous organ system–based medical conditions seen in our ICUs is well beyond the scope of a single issue of Seminars, more appropri-ately filling several thousand pages and hundreds of chapters typical of current major textbooks on critical care medicine Nevertheless, we have identified a cross-section of key topics and have solicited state-of-the-art reviews by highly qualified experts
Starting at the top, so to speak, Dr Bleck presents
a discussion of neurological complications of critical illness, with particular emphasis on metabolic encepha-lopathies, seizures, and neuromuscular conditions Drs
Miller and Ely share their current understanding of the rapidly evolving areas of delirium and cognitive dysfunc-tion in the ICU Drs Tarditi and Hollenberg present a structured approach to the ICU patient who has cardiac arrhythmias, emphasizing the challenges of managing tachyarrhythmias, whereas Dr Axler discusses the eval-uation and management of shock Drs Rinella and Sanyal provide a comprehensive review of acute hepatic failure as well as acute complications of chronic advanced
1
Division of Pulmonary and Critical Care Medicine, Virginia
Com-monwealth University Health System, Richmond, Virginia.
Address for correspondence and reprint requests: Curtis N Sessler,
M.D., Division of Pulmonary and Critical Care Medicine, Box 980050,
Virginia Commonwealth University Health System, Richmond, VA
23298-0050 E-mail: csessler@hsc.vcu.edu.
Non-pulmonary Critical Care: Managing Multisystem Critical Illness;
Guest Editor, Curtis N Sessler, M.D.
Semin Respir Crit Care Med 2006;27:199–200 Copyright # 2006
by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York,
NY 10001, USA Tel: +1(212) 584-4662.
DOI 10.1055/s-2006-945524 ISSN 1069-3424.
199
Trang 2liver disease Drs Weisbord and Palevsky examine acute
renal failure, including sections on epidemiology, causes,
prevention, and management
Drs Raghavan and Marik present an in-depth
review of adrenal insufficiency and the many issues
related to hyperglycemia and glycemic control in the
ICU Drs Mercer, Macik, and Williams expertly
ad-dress hematological disorders in the ICU, with particular
emphasis on thrombocytopenia and bleeding disorders
Drs Afessa and Peters provide a practical framework for
evaluating and managing the many serious infectious
and non-infectious complications related to
hemato-poietic stem cell transplantation Drs Bearman, Munro,
Sessler, and Wenzel conclude with a comprehensive
overview of infection control and prevention of nosoco-mial infections in the ICU, with emphasis on ventilator-associated pneumonia and catheter-related bloodstream infection
I would like to acknowledge the amazing exper-tise, attention to detail, and hard work of the authors of these articles, and convey my thanks for the steady hand
of the Seminars Editor-in-Chief, Joseph P Lynch, III, M.D., and the understanding and support of my wife and children, in creating this issue of Seminars
Curtis N Sessler, M.D
Guest Editor1
Trang 3Neurological Disorders in the Intensive Care
Unit
Thomas P Bleck, M.D., F.C.C.M.1,2,3
ABSTRACT
Neurological problems are common among critically ill patients; they often signal that other organs are failing, but are themselves important causes of morbidity and mortality Cognitive function may suffer as a consequence of septic encephalopathy, the pathophysiology of which is poorly understood; however, the affected patients usually return to their baseline when sepsis resolves Seizures and cerebrovascular disorders are also common in the intensive care unit Neuromuscular complications are important causes of failure to wean from mechanical ventilation and lead to substantial long-term morbidity
syndrome, critical illness myopathy, critical illness polyneuropathy, fulminant hepatic failure, seizure, septic encephalopathy
Many conditions encountered in intensive care
affect the nervous system The onset of an abrupt
neuro-logical complication is frequently obscured by the effects
of the primary illness (e.g., metabolic encephalopathy
may delay the recognition of an intracerebral
hemor-rhage) or its treatment (such as sedation to allow greater
synchrony with a ventilator) Other neural problems,
such as critical illness polyneuropathy, may develop
insidiously and become apparent only as the patient
improves At times the neurological problem has been
visible, but its manifestations may be inappropriately
attributed to the presenting illness.1 The intensivist
should be perspicacious about changes in level of
con-sciousness or movement when investigating a fall in
oxygen saturation or a rising white blood cell count.2
EPIDEMIOLOGY
Isensee et al evaluated neurological problems in 100
consecutive medical intensive care unit (ICU) patients
within 72 hours of admission.3 The study included all patients in need of intensive care except those with primarily cardiac disorders Eighteen were admitted for acute neurological disease and five others for encephal-opathy caused by drug overdose Of the remaining 67, 33% had a neurological complication of their medical conditions (11 metabolic encephalopathy, four hypoxic-ischemic encephalopathy [HIE], and seven other neuro-logical problems) Fifty-nine percent of the patients with neurological complications died, compared with 20% of the nonneurological patients
At the same time, we performed a 2-year pro-spective study of neurological complications among medical intensive care unit (MICU) patients to describe the neurological complications encountered and to iden-tify their effects on mortality and length of stay (LOS).4 Patients with a primarily neurological reason for admis-sion to the MICU were excluded from analyses of mortality and LOS; more than half of this group had ischemic stroke or intracranial hemorrhage The others
Departments of1Neurology,2Neurological Surgery,3Internal Medicine,
University of Virginia School of Medicine, Charlottesville, Virginia.
Address for correspondence and reprint requests: Thomas P Bleck,
M.D., University of Virginia School of Medicine, Neurology 800394,
McKim Hall 2025, Charlottesville, VA 22908-0394 E-mail: tbleck@
virginia.edu.
Non-pulmonary Critical Care: Managing Multisystem Critical Ill-ness; Guest Editor, Curtis N Sessler, M.D.
Semin Respir Crit Care Med 2006;27:201–209 Copyright # 2006
by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York,
NY 10001, USA Tel: +1(212) 584-4662.
DOI 10.1055/s-2006-945531 ISSN 1069-3424.
201
Trang 4were classified as having a complication of a critical
illness if they developed a neurological problem from a
medical disorder or its treatment We collapsed the
medical diagnoses into four categories: (1) sepsis,
in-cluding bacteremia with shock, the sepsis syndrome,
and the acute respiratory distress syndrome (ARDS);
(2) acute coronary artery disease; (3) other cardiac
disorders; and (4) all other patients (e.g., ventilatory
failure, gastrointestinal hemorrhage, hypotension not
assigned to another category) Patients with
neuro-logical complications were further divided into those
with metabolic encephalopathies, seizures,
cerebrovas-cular disorders, hypoxic-ischemic encephalopathy, or
other global brain disorders These latter categories
were not mutually exclusive Patients with clinically
apparent peripheral nervous system disorders were
in-cluded in the ‘‘other’’ group
We studied 1850 consecutively admitted patients;
of these, 92 (4.9%) were admitted for a primary
neuro-logical reason Of the remaining 1758 patients, 217
(12%) experienced neurological complications of their
underlying medical disease (Table 1) Table 2 details
the neurological complication rates by admission
cate-gory The mortality rate for all MICU patients was 32%,
but it was 55% for the 217 patients with neurological
complications, compared with 29% for those without
neurological complications Patients with neurological
complications also had significantly longer MICU and
hospital stays
Metabolic encephalopathy was the complication
most frequently encountered, seen in 62 patients Of
these, septic encephalopathy, without evidence for sig-nificant hepatic or renal dysfunction or hypoxemia, was most common The frequencies of different forms of metabolic encephalopathy are detailed in Table 3 Seiz-ures occurred in 61 patients, most often in patients with vascular lesions Hypoxic-ischemic encephalopathy oc-curred in 51 patients; in 27, the cause was primarily cardiac, with pulmonary disease accounting for the re-maining 24
Forty-eight patients suffered strokes while in the MICU Thirty-two of these were ischemic infarcts, 14 were intracerebral hemorrhages, and two were subar-achnoid hemorrhages Thirteen stroke patients had an identified cause other than arteriosclerosis, including underlying autoimmune diseases and bacterial endocar-ditis Stroke occurred in only 1% of patients with acute myocardial infarction This was less than the usually cited range of 1.7 to 2.4%.5,6
SEPSIS AND SEPTIC ENCEPHALOPATHY During the past 40 years, clinical analyses and investiga-tions of cytokine mechanisms have markedly improved our understanding of the causes and pathogenesis of sepsis.7Although bacteremia was previously considered
to be the sine qua non of systemic disease, occurring as a consequence of local infection, many patients suffer the same vasomotor disturbances and organ dysfunctions without positive blood cultures The foregoing epidemio-logical data indicate that septic encephalopathy is the most frequent neurological disorder encountered in
Table 1 Neurological Complications Encountered in 217
Patients at Risk with Severe Medical Illnesses in the
Medical Intensive Care Unit
Complication N (percent of patients
with diagnosis)*
Metabolic encephalopathy 62 (28.6)
Seizures 61 (28.1)
Hypoxic-ischemic encephalopathy 51 (23.5)
Stroke 48 (22.1)
Other diagnoses 50 (23.0)
*A single patient could have more than one complication; therefore,
the total number in this column exceeds the total number of patients.
Modified from Bleck et al 4
Table 2 Neurological Complication Rates by Primary Medical Intensive Care Unit Admission Category
Percent of Patients with Complications Category Seizure Vascular HIE Metabolic Other Sepsis 11 6 10 21 11 Other medical condition 4 3 4 3 6 Coronary artery disease 1 1 1 1 1 Other cardiac condition 4 3 3 2 4
4
Table 3 Etiologies of Metabolic Encephalopathy in a Medical Intensive Care Unit Population
Hypertensive 7 Hyperosmolar 4 Hypoglycemic 3
Modified from Sprung et al 12
Trang 5medical intensive care; it is also one of the more poorly
recognized and understood Septic encephalopathy was
described in 18278but has only recently become a subject
of organized neurological interest Young and coworkers
provided a thorough prospective analysis of this disorder
in a large university ICU.9This group required fever and
a positive blood culture for inclusion in their study, a very
restrictive definition of sepsis, which provided a
homo-geneous group for analysis Patients were excluded for
preexisting brain disease; frequent sedative or opiate
administration; pulmonary, hepatic, or renal failure;
en-docarditis; or long bone fractures that might have
pro-duced fat embolism
These workers identified 69 patients over 31
months; by clinical examination, 20 of them were not
encephalopathic (NE), 17 were mildly encephalopathic
(ME), and 32 were severely encephalopathic (SE)
Pa-tient age, blood pressure on entry into the study, and
temperature did not vary significantly among the groups
The lowest systolic and diastolic blood pressures were
statistically significantly lower (but probably not
biolog-ically significantly lower) in the ME and SE groups when
compared with the NE group Mortality depended on the
category of encephalopathy: none of the NE patients
died, whereas 35% of the ME and 53% of the SE patients
died Several laboratory values showed a linear
relation-ship with the severity of encephalopathy, including white
blood cell count, PaO2, blood urea nitrogen (BUN),
creatinine, bilirubin, alkaline phosphatase, and
potas-sium The serum albumin concentration was inversely
related to encephalopathy cerebrospinal fluid (CSF)
protein content was mildly elevated (60 to 85 mg/dL)
Electroencephalographic abnormalities are more sensitive
indicators of central nervous system (CNS) dysfunction
than the clinical examination, and also a powerful
pre-dictor of survival.10Evoked potential studies suggest that
brain dysfunction is even more prevalent in sepsis, being
abnormal in 84%.11 A Veterans Administration (VA)
cooperative sepsis study also showed that ‘‘alterations in
mental status are common in septic patients, and are
associated with significantly higher mortality.’’12
Eidelman and colleagues studied 50 patients with
severe sepsis and showed that encephalopathy was
asso-ciated with bacteremia and hepatic dysfunction.13 The
severity of encephalopathy correlated with mortality
PATHOLOGY AND PATHOPHYSIOLOGY
The pathological basis of septic encephalopathy remains
obscure Jackson et al autopsied 12 patients dying after
severe, prolonged sepsis.14 They found cerebral
micro-abscesses in eight patients and proliferation of astrocytes
and microglia in three others; these findings suggested
metastatic infection Three of these patients also had
central pontine myelinolysis, and three had ischemic
strokes The remaining patient demonstrated only
pur-puric lesions Eight of the patients had electroencepha-lograms (EEGs), three of which showed multifocal epileptiform activity Pendlebury and associates identi-fied 35 patients with multiple CNS microabscesses among 2107 consecutive autopsies.15All these patients had chronic, usually immunocompromising, diseases, and were frequently septic before death The most common organisms implicated were Staphylococcus aureus and Candida albicans In contrast, we did not find microabscesses in four patients autopsied of our 14 fatal septic encephalopathy cases; this may represent sampling error or other differences in the populations studied.4 The pathophysiology of septic encephalopathy is
of great interest The systemic mediators of inflamma-tion are capable of damaging the blood–brain barrier.16 Such disruption has been documented in an animal model early in sepsis.17 The behavioral effects of cyto-kines vary with the neuroanatomical structures affected but include thermogenic behaviors in the hypothala-mus18 and somnolence in the locus caeruleus.19 Inter-ferons also alter individual cortical and hippocampal neuronal functions, suggesting a myriad of effects on memory and emotion.20 Brain catecholamine concen-trations are decreased in experimental sepsis.21 Sepsis leads to the release of S-100B, a protein predominantly expressed in CNS glial cells, into the systemic circula-tion; this leakage was not affected by steroids in a human trial.22 Increased serum concentrations of S-100B are usually viewed as evidence of cellular damage, which may not be reparable
Cerebral blood flow (CBF) and cerebral oxygen extraction decrease in septic encephalopathy,23 along with the development of cerebral edema and disruption
of the blood–brain barrier.24Preliminary human studies suggest that these problems occur in several gray matter structures of the brain.25,26 Failure of cerebrovascular autoregulation is likely to compound these disorders,27 producing cerebral ischemia Both cerebral edema and blood–brain barrier disruption appear to correlate with damage to astrocytic foot-processes.28,29 Aquaporin-4 expression increases in septic encephalopathy, but the cellular events that trigger this change in sepsis require further research.30
The cause of the changes in CBF and oxygen extraction are less well understood Focal elevations in intracellular free calcium may cause neuronal dysfunc-tion and also contribute to apoptotic31 or necrotic cell loss.32 Activation of adenosine A1 receptors may be important in the development of a local CNS inflam-matory response.33Although cytokines have been sug-gested as mediators, a study of the effects of tumor necrosis factor was unable to confirm its role in this regard.34 However, a decline in CSF ascorbic acid concentration may reflect difficulty in safely handling the oxygen-derived free radicals potentially resulting from both cytokine and nitric oxide excess.35 These
NEUROLOGICAL DISORDERSIN THEICU/BLECK 203
Trang 6radicals may interfere with the mitochondrial electron
transport chain, leading to cellular energy deprivation.36
Magnesium administration may be able to attenuate
some of these problems,37 although this remains to be
demonstrated in humans
Abnormal systemic metabolism in sepsis may also
contribute to CNS dysfunction Mizock et al
demon-strated altered phenylalanine metabolism (elevated blood
and CSF levels, and elevated phenylalanine metabolites)
in 11 patients with septic encephalopathy; in contrast,
patients with hepatic encephalopathy had elevated CSF
concentrations of many other aromatic amino acids.38
Sprung and coworkers found elevated serum levels of
phenylalanine, ammonia, and tryptophan in
encephalo-pathic patients compared with infected patients with
normal sensoria, along with lower concentrations of
isoleucine.39 Other studies have confirmed this, and
find it linked to concentrations of calcitonin precursors
and interleukin-6.40The significance of these correlative
studies for the pathogenesis of encephalopathy is
un-certain Several authors have tried to implicate abnormal
hepatic and muscular metabolism of aromatic amino
acids in both hepatic and septic encephalopathies, but
this hypothesis has been challenged (see further
discus-sion in the next section) Antibiotic treatment of septic
patients may actually enhance these problems.41
Septic patients are prey to a wide variety of other
metabolic disorders and intoxications that cause
ence-phalopathy apart from the direct effects of sepsis on the
brain and on cerebral blood flow.42Nonconvulsive status
epilepticus is an underrecognized problem in the
pop-ulation at risk.43 There is neither a diagnostic test to
discriminate sepsis from other causes of encephalopathy
nor a specific treatment for the CNS disturbance From a
clinical standpoint, the diagnosis of septic
encephalop-athy remains one of exclusion.44
Hepatic Failure and the Central Nervous System
The current debate over the pathogenesis of hepatic
encephalopathy is of great importance to clinical
neuro-scientists In fulminant hepatic failure (FHF), increased
intracranial pressure (ICP) has become a major cause of
death in patients awaiting transplantation.45 Patients
whose ICP has been elevated may survive a transplant
but be left with CNS deficits.46
The mechanism of the cerebral edema that
devel-ops in FHF appears to be related to mitochondrial
dysfunction47; it requires aggressive treatment.48
Ste-roids are not effective, but mannitol has been useful.49
As in many other causes of brain edema, abnormal
function of matrix metalloproteinases probably
contrib-utes to the problem.50As with most other causes of brain
edema, aquaporin-4 expression is involved; it may be
possible to decrease this by the administration of
calci-neurin antagonists.51
Hyperventilation had previously been thought to increase mortality, but a controlled trial demonstrated its utility.52High-dose barbiturates may be used if mannitol and hyperventilation fail to control ICP.53The effect of posture is unpredictable,54 and computed tomographic (CT) scanning is debated as an indicator of the severity
of intracranial hypertension.55,56Attempts to lower ICP
by reducing extracellular volume through hemofiltration have not been effective.57Dialysis against albumin may hold more promise.58There is no current substitute for invasive ICP monitoring in patients with FHF who are
in grade 3 (stuporous) or grade 4 (comatose) The need for monitoring extends through the liver transplant operation into at least the first postoperative day.59 Recombinant factor VII administration immediately before ICP monitor placement appears to reduce the risk of intracerebral hemorrhage.60
Patients with FHF may also have elevated levels
of apparently endogenous 1,4-benzodiazepines,(3) which may explain stupor or coma in patients who do not have ICP elevations An interaction between gamma-amino butyric acid (GABA) and elevated con-centrations of ammonia may be important in both FHF and more chronic forms of hepatic encephalopathy.61 More recent work has concentrated on the putative role
of neurosteroid agonists of the benzodiazepine recep-tor62because researchers have been unable to identify a compound that structurally resembles the pharmaceut-ical benzodiazepine nucleus
Chronic hepatic encephalopathy does not appear
to cause ICP elevation unless intracranial bleeding supervenes As in FHF, endogenous benzodiazepine-like compounds (GABAA agonists) likely play a major role,(4) and the use of GABA antagonists is being actively investigated but has not yet become standard practice About 70% of chronic hepatic encephalopathy patients awaken rapidly when given flumazenil (for the duration of the drug’s effect).63,64 These patients have numerous other metabolic abnormalities that may con-tribute to their encephalopathy, including abnormalities
in the Krebs cycle65and of methionine metabolism.66
OTHER CAUSES OF ENCEPHALOPATHY IN THE INTENSIVE CARE UNIT SETTING Renal and hypoxic encephalopathies are quite common
in the ICU environment Details of their diagnosis and management are beyond the scope of this article, and have been reviewed.67
Iatrogenic causes of encephalopathy are also com-mon in ICUs and should be actively excluded Hypno-sedative drugs and narcotic analgesics are the most common agents in this category Flumazenil and nalox-one will reverse these drug-induced encephalopathies The need to reverse the effects of these drugs in an individual ICU patient should be carefully assessed
Trang 7because the emergence of agitation or severe pain may be
detrimental to the patient If these drugs are used to
determine whether encephalopathy is due to
medica-tions, doses much smaller than those to treat respiratory
depression should be used initially Flumazenil (0.1 to
0.2 mg intravenously over 15 seconds), may be given
every 60 seconds to a maximum of 1.0 mg The risk of
seizures is always present when this drug is
adminis-tered.68 Naloxone, 0.04 to 0.08 mg intravenously, may
be given every 60 seconds to a total dose of 0.8 mg
Barbiturates are not antagonized by available agents It
should be apparent from the preceding section on
hepatic encephalopathy that a response to flumazenil is
not specific for a benzodiazepine overdose
Other encephalopathic conditions may arise
dur-ing the course of ICU treatment One of our poorly
nourished patients developed Wernicke’s
encephalop-athy from the dextrose administered as the vehicle for a
lidocaine infusion to treat ventricular arrhythmias after
an acute myocardial infarction The clinician must
al-ways be aware that admission to the ICU does not
prevent the development of intercurrent illnesses
Seizures in the Intensive Care Unit
In our epidemiological study, 34 patients had simple
partial seizures (with or without secondary
generaliza-tion), and six had complex partial seizures (with or
without secondary generalization).4 Twenty patients
had seizures that appeared to be generalized at onset,
and six patients developed status epilepticus in the
MICU; all required at least two agents to terminate
their status (usually a benzodiazepine and phenytoin)
Two of these patients developed refractory status
epi-lepticus and were treated with pentobarbital coma
Three patients were admitted to the MICU for
refrac-tory hypotension after receiving phenytoin infusions at
rates between 25 and 50 mg/min The blood pressures of
these patients did not improve with fluid resuscitation
alone; all required dopamine infusions for several hours
to maintain blood pressure and systemic perfusion
In contrast to our experience in other hospitalized
patients, the focal onset of partial seizures with
secon-dary generalization was usually noted and adequately
described This was a useful guide to management
because patients with partial seizures generally
experi-enced seizure recurrence and thus probably benefited
from anticonvulsant treatment.69
The diagnosis and management of seizures
should be pursued differently in ICU patients than in
other patients We had hoped to develop rules to predict
which patients having seizures in the ICU might be
evaluated without imaging procedures, but were unable
to do so because most patients had vascular or infectious
causes for their seizures All patients experiencing a
single seizure in the ICU were treated with some form
of anticonvulsant therapy; this was often justified by the argument that their underlying medical condition might
be adversely affected by subsequent seizures We believe that this constitutes excessively aggressive management and that it postpones an appropriate search for etiology
For example, all three patients with recurrent seizures caused by nonketotic hyperglycemia were treated with at least two anticonvulsants; these drugs are known to be ineffective in this condition.70
When ICU patients do require treatment, phe-nytoin remains a reasonable first choice However, a second agent, usually phenobarbital, was required in most patients Lorazepam was useful for the suppression
of breakthrough seizures, but the use of this drug was often continued without adequate attention to optimal use of phenytoin or phenobarbital
Pentobarbital coma is often considered the treat-ment of choice for refractory status epilepticus in ICU patients We have adopted the use of high-dose mid-azolam in this circumstance.71This method appears to
be more rapidly effective and to have substantially fewer and less severe adverse effects than pentobarbital, thio-pental, or propofol.72
NEUROMUSCULAR COMPLICATIONS
OF SEPSIS Although recognized by earlier authors such as Osler, the modern era of interest in this problem began with the independent reports of three groups reported by Rivner
et al (four patients),73Bolton et al (17 patients),74and Roelofs (four patients).75Bolton’s group followed their initial description with a series of papers that character-ized the clinical,76electrophysiological,77and patholog-ical aspects of critpatholog-ical illness polyneuropathy.78Although many other groups have made significant contributions
to this area (e.g., Op de Coul et al),75the work of Bolton and his colleagues is in great measure responsible for the recognition of this problem among intensivists More recent work continues to show a high incidence of this condition.79
These neuromuscular complications are presently categorized anatomically Critical illness polyneuropathy
is an axonal disorder affecting both sensory and motor nerves.78Electrophysiological evidence of this condition,
as already noted, is present in 70% of septic patients, but the percentage with weakness sufficient to impede ventilator weaning or ambulation is less The phrenic nerves are typically the most severely involved Neuro-muscular junction (NMJ) dysfunction in the setting of critical illness is typically a consequence of a prolonged effect of NMJ blocking agents, usually because of im-paired clearance.80Myopathy in critically ill patients is most commonly seen in those who have received NMJ blocking agents and corticosteroids in the treatment of severe asthma.81 Although this has been reported most
NEUROLOGICAL DISORDERSIN THEICU/BLECK 205
Trang 8commonly after vecuronium use, it also occurs after NMJ
blocking agents that do not depend on renal or hepatic
excretion (e.g., atracurium).82Myopathy may also occur
in the setting of some viral infections, such as influenza
A syndrome of disseminated pyogenic myopathy has also
been described,83 presumably as a consequence of
bac-teremic seeding of muscles
Critical illness polyneuropathy has also been
noted after organ transplantation without sepsis.84
Although most of the patients reported to have critical
illness polyneuropathy have been adults, this condition
has been recognized with increasing frequency in
chil-dren as well.85
In contrast to the body of experimental work on
septic encephalopathy, very little is understood about the
pathogenesis of the neuromuscular complications of
sepsis.86Hyperglycemia correlates with the development
of critical illness polyneuropathy, but these may be
independent markers of disease severity However, the
dramatic reduction in critical illness polyneuropathy
with intensive control of blood glucose in both medical87
and surgical88ICU patients points to an important role
of hyperglycemia in the genesis of this condition, as well
as in many other neurological problems seen in critical
care units.89The neuronal microenvironment is similar
to that of the extracellular space of the brain; the same
alterations that produce septic encephalopathy may be
responsible for critical illness polyneuropathy, but
fur-ther investigation is clearly needed Critical illness
myo-pathy may result from the functional denervation
induced by NMJ blockade; it does not appear to be
simply a severe form of steroid myopathy
Diagnosis, Differential Diagnosis, and Prognosis
Recognition of a neuromuscular complication of sepsis
generally occurs as the patient begins to recover from the
critical illness that first required ventilatory support
Critical illness polyneuropathy is usually suspected
when the patient’s pulmonary mechanics (e.g., static
compliance) and gas exchange suggest that weaning
should be possible, but the patient is too weak to tolerate
it.90There is commonly some evidence of distal
weak-ness on examination Tendon reflexes are often absent or
diminished, but critical illness polyneuropathy may be
present without alteration in reflexes.91Gorson provides
an excellent framework for the evaluation of patients
with these problems.92
The diagnosis depends on electrophysiological
studies, which demonstrate an axonal disorder
Electro-myographic studies of the diaphragm confirm the
pres-ence of denervation.93 The differential diagnosis is
usually limited to consideration of the axonal form of
the Guillain-Barre´ syndrome; this condition usually
causes much more severe generalized weakness than
critical illness polyneuropathy, and typically causes an
increased cerebrospinal fluid protein concentration An-tecedent infection with Campylobacter jejeuni is fre-quently in patients with the axonal form of Guillain-Barre´.94Other differential diagnostic concerns are bot-ulism, which impairs presynaptic acetylcholine release, and myasthenia gravis, in which the motor end plate is damaged These conditions have characteristic nerve conduction and electromyographic characteristics No specific treatment for critical illness polyneuropathy is available Anecdotal evidence does not favor the use of plasma exchange or intravenous immunoglobulin, but there have been no definitive trials Almost all patients recover eventually, but this may require 6 months or more of ventilatory support
The prolonged effect of NMJ blocking agents can
be suspected by lack of tendon reflexes and inability to produce muscle contraction with a bedside neuromus-cular stimulator If the diagnosis is in question, it can be confirmed by formal nerve conduction studies and elec-tromyography There is no specific treatment, but the condition will resolve when the agent in question has cleared
Critical illness myopathy is often accompanied by substantial elevation of the serum creatine kinase (CK) concentration, which serves to distinguish this condition from steroid myopathy, in which the CK is usually normal Electromyography is usually an adequate diag-nostic study, and muscle biopsy is only rarely required.95 Again, no specific treatment is available, but the con-dition will resolve; whether it will resolve faster if systemic steroids are reduced or discontinued is uncer-tain A more recently described syndrome of acute quadriplegic myopathy is also probably associated with steroids; in this condition, muscle is electrically inexcit-able even with direct stimulation.96Nerves are histolog-ically normal, but muscles show thick filament loss.97 Although no treatment is known, the prognosis for this condition is for more rapid recovery than that for critical illness polyneuropathy
There are many other neurological problems that may arise during the course of an ICU stay which may impede weaning from mechanical ventilation Kelly and Matthay prospectively studied 66 consecutive adult pa-tients requiring mechanical ventilation for more than
48 hours to determine the reasons for their ventilatory problems.95 Neurological problems, primarily encepha-lopathies, were held responsible for the continuing need for ventilatory support in 32% of the patients, and contributed to this problem in another 41% Although this study was not directed at patients who failed to wean after resolution of their presenting disease, it does high-light the role of neurological problems early in critical illness Spitzer and colleagues studied 21 patients who failed to wean after their presenting disease had im-proved to the point that their intensivists believed that mechanical ventilation should no longer have been
Trang 9necessary.98 Thirteen (62%) of these patients had a
neuromuscular disorder that was either the major cause
of or contributed substantially to their ventilatory
prob-lems Only seven of these 13 patients had critical illness
polyneuropathy; other neuropathic conditions and
un-suspected motor neuron disease were also uncovered
Most intensivists will also be familiar with the less
common acute myopathies which may complicate
crit-ical illnesses, especially in patients who have received
neuromuscular junction blockade.99
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