Delirium

Delirium is defined in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders as a disturbance of consciousness and cognition that develops over short period of time (hours to days) and fluctuates over time.
Many different terms have been used to describe the syndrome of cognitive impairment in critically ill patients include:
ICU psychosis, acute confusional state, ICU encephalopathy and acute brain syndrime. However, ICU delirium is the preferred term.
Important of delirium:
ICU delirium has been demonstrated to be an independent predictor of the length of hospital stay as well as ICU and 6-month mortality rates.
As many as 70-80% of ICU patients experience delirium. It is the most common mental disorder among elderly patients in the ICU. Sleep deprivation, sepsis, hypoxaemia, use of physical restrains, fluid and electrolytes imbalances, and metabolic and endocrine derangements have been implicated in the causation of delirium. On average, ICU patients sleep only 2 hours/day and less than 6% of their sleep is REM sleep.
Delirium is characterised by fluctuating disturbance of consciousness, cognition, concentration, memory and attention. Delirium can be categorised into subtypes according to psychomotor behaviour. Hypoactive delirium is characterised by decreased responsiveness, withdrawal and apathy. Whereas, hyperactive delirium is characterised by agitation, restlessness, and emotional liability.
Peterson and coworker observed that in a cohort of ICU patients; pure hyperactive delirium was rare (1.6%). In contrast, 43.5% of patients had purely hyperactive delirium and 54.1% had mixed delirium.

Mneumonics for Clinical Picture
Disordered thinking
Euphoria, fearful, depressed or angry
Language impaired
Illusions/delusions/hallucinations
Reversal of sleep-wake cycle
Inattention
Unaware/disoriented
Memory deficit

Important aetiologies of delirium:

Demented or elderly/Disturbed sleep/Dehydration
Electrolyte disturbance/Emotional stress
Lung or Liver failure
Intubation and ventilation
Renal failure
Infection/Injury
Use of catheters (e.g. venous or bladder) or physical restrains
Metabolic problems (e.g. thyroid)/Medication/Malnutrition

Delirium Assessment:
The Intensive Care Delirium Screening Checklist (ICDSC) being the most validated. It is an eight item delirium checklist (Bergeron, Intensive Care Medicine 2001).
The score of 1 is given if each of the following elements is met:
1. Altered level of consciousness: -non-responsive, poorly responsive, drowsy, or hypervigilant
2. Inattention -difficulty following instruction, cannot focus
3. Disorientation
4. Hallucinations, delusions, or psychosis
5. Psychomotor agitation or rertardation - hypo or hyper activity
6. Inappropriate speech or mood -inappropriate, disorganised or incoherent speech or inappropriate display of emotion
7. Sleep-wake cycle disturbance -sleep less than 4 hours or waking frequently at night
8. Symptom fluctuation
A SCORE OF 4 OR MORE IS CONSIDERED INDICATIVE OF DELIRIUM.
==> All patients should be regularly screened (8 hourly) for the presence of delirium.
The second validated tool is Confusion Assessment Method for the ICU (CAM-ICU) which is easy to use and requires minimal training.

Management:
1. Patient orientation and preservation of the sleep-wake cycle are important to minimise the risk of delirium.
2. Sedation with benzodiazepines should be avoided. Benzodiazepines SHOULD NOT be used for the treatment of delirium.
3. Dexmedotemidine is a promising drug for the prevention and treatment of delirium.
4. Haloperidol is recommended as the drug of choice for the treatment of delirium by the society of critical medicine (SCCM) and the American Psychiatric Association.
5. Melatonin has been suggested to reset the internal circadian rythm and sleep-wake cycle and may have a role in the treatment and prevention of delirium in ICU patients. Bourne and colleagues demonstrated that melatonin given at night increased the duration of sleep. The recommended dose is 2 mg.

interesting website: www.icudelirium.org

THE ENCEPHALOPATHIC PATIENT IN ICU

Encephalopathy: alteration in the level or content of consciousness due to a process extrinsic to the brain.
Metabolic encephalopathy in particular that related to sepsis is the most common cause of ALOC in the ICU setting.

AETIOLOGY:
Hepatic failure
Renal Failure
Respiratory Failure
Sepsis- sepsis associated encephalopathy
Electrolyte abnormalities: hypo and hyper Natraemia, hypercalcaemia
Hypoglycaemia and hyperglycaemia
Acute pancreatitis
Endocrine -addisonian crisis, myxoedema coma, thyroid storm
Drug withdrawal -benzodiazepines, opiates
Hyperthermia
Toxins: alcohols, glycols, TCAs
Intensive care unit syndrome
D lactic acidosis

Distinguishing features of structural and metabolic encephalopathy:
STRUCTURAL:
1. state of consciousness -usually fixed level of depress conscious state, may deteriorate progressively
2. Fundoscopy -maybe abnormal
3. Pupils -may be abnormal in size or response to light
4. Eye movements -may be affected
5. Motor findings -asymmetrical involvement
6. Involuntary movements -not common

METABOLIC
1. State of consciousness -milder alteration of conscious state, waxing and waning of altered sensorium
2. Fundoscopy - usually normal
3. Pupils - usually preserved light response although pupils shape and reactivity affected in certain overdose
4. Eye movements - usually preserved
5. Motor findings -abnormalities usually symmetrical
6. Involuntary movements -asterixis, tremor, myoclonus frequently seen

OMG, that is not pseudohyponatraemia!

One fine day during my rounds (on public holiday, the Chinese New Year), my junior medical doctor asking me whether to correct the patient's Na of 120 or not because one of the nephrology doctors said that the patient is actually having pseudohyponatraemia. I asked him back, a little bit excited " Wow, since when the hospital is able to measure serum osmolality?" In a confused manner he showed me the entered notes:
"Calculated patients's osmolarity is 290 i.e. 2 (120) + glucose (10) and BUN of 40. Therefore this patient has pseudohyponatraemia"
I was taken aback, and said "OMG, that is NOT pseudohyponatraemia!" Later, I attempted to explain to him and my interns about the classification of hyponatraemia, definition of pseudohyponatraemia and the meaning of effective osmolarity. Since he is a very junior doctor and he was bewildered with my explanation, I decided to stop my bedside teaching at that point. Furthermore, that was my first patient (out of twelve) on a public holiday ICUrounds. I reassured him that I will discus this issue later.

The background of my hospital: I am working in one of the public hospitals in Malaysia (general hospital) and don't you believe it our lab has no facility to measure serum and urine osmolality! Very Very Frustrating..
Back to the issue above, there are a couple of questions to be answered:
1. How is hyponatraemia classified?
2. What is the corrected osmolality?
3. Types of hyponatraemia in advanced renal failure?
4. And that will lead to the main question, either to treat the hyponatraemia or not.
Yes, let us back to basics

Calculated osmolarity= 1.86 x ( [Na] + [K] ) + [glucose] + [urea]


Hyponatraemia

Hyponatraemia is defined as serum sodium of less than 135 mmol/l and may be classified as isotonic, hypertonic or hypotonic, depending upon the MEASURED osmolality.
In evaluation of hyponatraemia, the history and physical examination should be directed toward identification of findings that are typical of the particular causes of hyponatraemia and assessment of volume status.
Three lab tests provide important initial information in the differential diagnosis of hyponatraemia:
1. Serum osmolality
2. Urine osmolality
3. Urine sodium concentration

Serum osmolality (Sosm)ranges from 275 to 290 mosmol/kg is reduced in most hyponatraemic patients because it is primarily determined by the serum Na concentration and accompanying anions.
In patients with advanced renal failure, the hyponatraemia is due to an inability to excrete water resulting from the impairment of renal function. Although this will tend to lower the Sosm, this effect is counterbalanced to a variable degree by the associated elevation in blood urea nitrogen (BUN) resulting in Sosm that may be normal or elevated.
However there is a difference between the measured serum osmolality and effective serum osmolality in patients with renal failure. In contrast to sodium and glucose, urea is an ineffective osmole, since it can freely cross cell membranes and therefore does not obligate water movement out of the cells. Thus, patients with hyponatraemia and renal failure have a low effective serum osmolality that becomes apparent if the measured Sosm is corrected for the effect of urea:
Corrected Sosm = Measured Sosm - BUN (mmol/L)
For this reason I prefer the classification according to the tonicity.

Tonicity:

Osmolality is a measure of the number of the osmol/kg of water. The osmolality of the ECF is due largely to sodium salts. Clinical effects of hyperosmolality, due to excess solute, depend upon whether the solute distributes evenly throughout the total body water (e.g. permeant solute of alcohol or urea) or distributes in the ECF only (e.g. impermeant solutes of mannitol or glucose). With impermeant solutes, hyperosmolality is associated with a shift of fluid from the ICF to the ECF compartment. Hyperosmolality due to increased impermeant solutes is known as hypertonicity.

Pseudohyponatraemia
Plasma normally contains 93% water and 7% solids (5.5% proteins, 1% salts and 0.5% lipids). If the solid phase is elevated significantly (e.g. in hyperlipidaemia or hyperproteinaemia), any device which dilutes a specific amount of plasma for analysis will give falsely lower values for all measured compounds. This effect produces "factitious hyponatraemia" or pseudohyponatraemia (since it represents a labarotary artefact) and is associated with a normal measured serum osmolality.
Thus a normal serum Na concentration of 142 mEq/l (measured per litre of plasma) actually represents a concentration in the physiologically important plasma water of 153/L (142 / 0.93 = 153). In patients with marked hyperlipidaemia or hyperproteinaemia, the proportion of the plasma that is water falls to a lower value. As a result, the sodium concentration per liter of plasma will fall, which is an artifact since the physiologically important sodium concentration per liter of plasma water is normal. Supposed that the plasma water constitute 80% of the plasma in a patient with hyperlipidaemia. The Na concentration of 120mEq/l (measured per L of plasma) would be corrected to 150mEq/l.
Many lab analysers measure Na with ion-selective electrodes which utilise indirect potentiometry in which the plasma sample is diluted before measurement. This analysers will report a low Na concentration. Ion selective electrodes will reveal a normal sodium concentration if an instrument employing direct potentiometry is used.
I hope this would explain why I was surprised with the conclusion made by that doctor from that particular (neprology) dept.

Disorders of consciousness

This week I am oncall and it is a long weekend, since the CNY was celebrated on Thursday. I am going to Adelaide for Tub's course in two weeks time and I'd better be prepared for that intensive course. I must have a proper study strategy. Apparently, it is very difficult for me to juggle my time to suit for family, social, work, research and department.

The above topic is one that I always review over and over again.

Care of the comatose patient
A: assessment of airway adequacy and the patients gag reflex, all of them at the risk of aspiration and there must be a low threshold for establishing a definitive airway. However, all traumatised patients should be assumed to have a potential cervical spine injury.
B: It is important to ensure optimal gas exchange
C: Goals of circulatory therapy include restoration of appropriate MAP and correction of dehydration/volume resuscitation.

The rest will be divided into SPECIFIC and NON SPECIFIC treatment. I am not going into details of the management.
Differrential diagnosis of coma:
A. coma with focal signs
1. trauma-extradural, subdural and parenchymal haemorrhage, concussions
2. vascular-intracerebral haemorrhage, thromboembolic
3. brain abscess

B. Coma without focal signs but with meningeal irritation
1. infection - meningitis, encephalitis,
2. SAH

C. Coma without focal signs and no meningeal irritation
1. metabolic causes - hypoNa, hypoglycaemia, hyperglycaemia, hypoxia, hypercapnea, hypo and hyperthermia, hypo and hyper osmolar states
2. endocrine causes - myxoedema, adrenal insufficiency, hypopituitarism
3. seizure disorders
4. organ failure - hepatic and renal
5. Toxic/drug - sedatives, narcotics, alcohol, psychotropic


Usefullness of EEG in coma1. Identification of NCSE
2. Diagnosis of hepatic encephalopathy
-Presence of paroxysmal triphasic waves
3. Assessing severity of hypoxic encephalopathy
- Presence of theta activity
- diffuse slowing
-Burst suppression (seen with more severe forms)
-Alpha coma (seen with more severe forms)
4. Herpes encephalitis
-Periodic sharp spikes

Anoxic coma

Cardiac arrest is the third leading cause of coma resulting in ICU admission after trauma and drug overdose. The clinical outcome depends on the severity and duration of oxygen deprivation to brain.

Clinical and labarotary predictors of unfavourable prognosis in anoxic coma:

1. Duration of anoxia (time interval between collapse and initiation of CPR) ===> 8-10 minutes
2. Duration of CPR (time interval between initiation of CPR and ROSC)===> > 30mins
3. Duration of anoxic coma ===> 72 hours
4. Pupillary reaction ===> absent on day 3
5. Motor response to pain (a motor response worse than withdrawal) ===> absent on day 3
6. Roving spontaneous eye movements ===> absent on day 1
7. Elevated neuron specific enolase (cytoplasm of neurons) > 33 microgram/l
8. SSEP recording ===> absent N20

Predictors of death or severe neurological impairment after submersion (near drowning)
1. At site of immersion:
i. immersion duration > 10 minutes
ii. delay in commencement of CPR > 10 minutes

2. In the emergency department
i. Asystole on arrival or CPR duration > 25 minutes
ii. Fixed dilated pupils and GCS < 15
iii. Fixed dilated pupils and arterial pH < 7.0

3. In the ICU
i. No spontaneous, purposeful movements and abnormal brainstem function 24 hours after immersion
ii. Abnormal CT scan within 36 hours of submersion

Comorbidities associated with delayed resolution of pneumonia

1. COPD
Impaired cough and mucociliary clearance
2. Alcoholism
Aspiration, malnutrition, impaired neutrophil function
3. Neurologic disease
Aspiration, impaired clearance of secretions and cough
4. Heart Failure
Edema fluid, impaired lymphatic drainage
5. Chronic Kidney disease
hypocomlementaemia, impaired macrophage and neutrophil function, reduced humoral immunity
6. Malignancy
Impaired immune function, altered colonization, effects of chemotherapy
7. HIV
Impaired cell mediated and humoral immunity
8. Diabetes Mellitus
Impaired neutrophil function and cell mediated immunity

Clinical Approach to the Septic Patient

Diagnosis For both community and hospitalised patients presenting with sepsis:

1. Diagnose or rule out mimics of sepsis by history, physical examination and routine lab tests


2. Initiate medical therapy appropriate for disorders mimicking sepsis


3. If mimics of sepsis are ruled out determine site of septic focus in critically ill patients presenting with sepsis, distinguish colonisation from infection in isolates from urine, respiratory secretions and noninfected wounds


4. Treat infection and avoid treating colonizing organisms

Interventions

A. Antibiotic interventions

i. Select empiric monotherapy based on coverage of predictable pathogens determined by focus of infection

ii. Select antibiotic with low resistance potential

iii. Select antibiotic witn a good safety profile

B. Non antibiotic interventions

i. Administer aggressive and effective intravascular volume replacement

ii. If pressors are needed, give volume replacement before pressors

iii. Restore normothermia with heating blanket

iv. Surgical intervention if sepsis is related to intra-abdominal organ perforation or obstruction or abscess. For infected devices, remove the device.

It is of paramount important to give fluid therapy before giving vasopressors. If the hypovolemia is not corrected promptly the patient will progress to a refractory shock state. By then the tissue perfusion would not respond to vasopressor drugs, even the blood pressure and intravascular volume were to be restored and cardiac output would remain depressed. The resultant lactic acidosis further depresses the myocardium and worsens the hypotension. The common complications of prolonged shock are massive bleeding, DIC and MODS which are often fatal.

Questions:

1. List the likely pathogens in gram negative sepsis in a patient who has been on meropenem for a week?

a. stenotrophomonas

b. MDR acinetobacter or pseudomonas

2. List the factors which result in failure in resolution of sepsis despite antibiotic therapy

• 
  
  wrong antibiotic choice


• 
  
  delayed administration of antibiotics


• 
  
  Inadequate source control


• 
  
  Inadequate antimicrobial blood levels


• 
  
  Inadequate penetration of the antimicrobial to the targer site


• 
  
  antimicrobial neutralization or antagonism


• 
  
  superinfection or unsuspected secondary bacterial infection


• 
  
  nonbacterial infection


• 
  
  noninfectious source of illness

pseudosepsis

Within last two weeks, I have diagnosed and treated 3 H1N1 pneumonia with ARDS. One who is severely obese (BMI>60), one pregnant lady who just had LSCS due to fetal distress and then a student who presented as acute exacerbation of bronchial asthma eventhough the last attack was more than 15 years ago. I used fluid restriction strategy with frusemide to keep even balance, according to FACTT trial and ARDS net ventilation strategy but with initial PEEP of 14-16cmH2O.
I have noticed in one patient, the WCC rised to more than 30,000 but her cultures were all negative. Anyway, I'd changed all of her lines. Her condition was alway stable with only low grade fever.
----------------
Pseudosepsis
-----------------
Conditions that mimic sepsis
Common disorders:
1. Diuretic induced hypovolemia
2. Acute GI hemorrhage
3. Acute PE
4. Acute MI
5. Acute (oedematous/necrotic) pancreatitis

Uncommon disorders:
1. Diabetic ketoacidosis
2. SLE flare
3. Relative adrenal insufficiency
4. Rectus sheath hematoma

Several conditions may present with acute abdominal pain accompanied by fever, leukocytosis with a left shift and hypotension mimicking intra-abdominal sepsis. Such patients may have SG catheter readings that are compatible with sepsis. These medical disorders include diabetic crisis in diabetic ketoacidosis, luetic crisis in patient with syphilis, right rectus syndrome in patients with EBV infectious mononucleosis, rectus sheath hematoma, acute porphyria, SLE flare involving the peritoneum, acalculous cholecystitis due to vasculitis, dissecting AAA, splenic rupture, and pseudoappendicitis due to yersinis enterocolitica or other organism. These medical mimics of acute intra abdominal sepsis are serious disorders, many of which have specific treatments.
The correct presumptive diagnosis is essential for effective therapy of sepsis as well as in the disorders mimicking sepsis.

Anion Gap

Approach to ABG analysis, the principles

1. Check arterial pH for net deviation
2. Assess the pattern
3. Look for associated clues
4. Assess the compensatory response
5. Check for additional indices for metabolic acidoses

If the patient has metabolic acidosis, determine whether it is normal anion gap or high anion gap metabolic acisosis. Correct the anion gap to patient's albumin level.
Look for mixed disorders e.g. mixed normal with HAG acidoses.
Important gap and other indices in ICU

1. Anion gap
2. Osmolar gap
3. Delta gap
4. Delta ratio
5. Lactate gap
6. Oxygen saturation gap
7. Urinary anion gap

Pearls and nonsense

• The absence of an anion gap does not exclude typical causes of anion gap acidosis, i.e. DKA may present without an anion gap.
• There is no identifiable cause of an HAG in 1/3 of patients.
• Large AG are most commonly DKA or lactic acidosis, less commonly ethylene glycol. Higher AGs correlate with increased severity of illness.
• Delta gap of > 2 - the presence of a mixed disorder is likely.

A reduced anion gap may be seen with :
-->Principle: decreased unmeasured anions, increased unmeasured cations and analytical errors.

• hypermagnesaemia
• hypercalcaemia
• Lithium toxicity
• Excess Immunoglobulins (multiple myeloma, intragam infusion)
• hypoalbuminaemia

Causes of elevated AG without acidosis:

• dehydration
• alkalosis
• sodium salts of unmeasured anions (citrate, lactate or acetate)
• certain antibiotics ( Na penicillin, carbenicillin)
• decreased in unmeasured cations (severe combined hypomagnesaemia, hypocalcaemia and hypokalaemia)

Define standard base excess (SBE): ?
ANION GAP: Anion gap is 'unmeasured anions, = (Na + K) - (Cl + HCO3)
Metabolic acidosis (reduced bicarb) must be associated with either an increased of the AG (HAG acidosis) or of the Chloride (NAG or hyperchloraemic) since the overall quantity of cations and anions must match bicarb loss from gut or kidney.With replacement by Cl- containing fluid will result in a non anion gap hyperchloraemic acidosis.