Differential diagnosis of weakness in ICU

Weakness in ICU is another common case during the clinical exam. I have found this in one of my books and I thought that it might be useful in helping me to organise my thought in synthesising the diagnosis during that time. Critically ill patient frequently have ICU myopathies and polyneuropathy. Weakness is common with SIRS and organ transplantation. Steroids, muscle relaxants and prolonged ventilation increase risk. MRI or CT scan, EMG and muscle biopsy may guide diagnosis.

1. Critical illness: - Clinical illness neuropathy, Myopathy of Intensive Care
2. Autoimmune: -Guillain-Barre syndrome, Myasthenia gravis, Dermatomyositis, Polymyositis
3. Nutritional: -Increased catabolism and wasting, undernutrition
4. Electrolyte disorders: -Phosphate, -Mg, K, Na
5. Endocrine disorders:-Hyper and hypo-thyroidism
6. Infection: -Botulism, poliomyelitis, tetanus, diphtheria, HIV, West Nile, Creutzfekdt-Jacob
7. Toxins: -Organophosphates, lead, tick paralysis, beliadonna
8. Drugs: -Muscle relaxants, steroids, magnesium, aminoglycosides, dapsone
9. CNS injury: -Stroke, spinal cord injury
10. Congenital: -Muscular dystrophy, periodic paralysis, motor neuron disease, spinal muscular atrophy, Tay-Sachs, Lower motor neurone syndromes, myotonia, acute intermittent porphyria
11. Metabolic: -alkalaemia
12. Paraneoplastic: Eaton Lambert syndrome, proximal myopathy

Causes of generallised muscle weakness, hyporeflexia and no sensory signs:

• Guillain Barre Syndrome
• Myasthenia Gravis
• Botulism
• Toxic Neuropathy : thallium, arsenic, hexane
• Acute intermittent porphyria
• Tick paralysis
• Lyme disease
• Poliomyelitis

Q: How would you differentiate a myopathy from a neuropathy clinically?

A: Distinguishing features:

1. Neuropathy

• site of weakness: distal
• sensory: may have concomintant sensory and signs
• reflexes: reflexes lost early
• fasciculations: may be present
• contractures: not a feature
• myocardial dysfunction: not a typical feature

2. Myopathy

• site of weakness: usually proximal
• sensory: usually pure motor
• reflexes: preserved until late
• fasciculations: not typical
• myocardial dysfunction: may have accompanying cardiac dysfunction witn the dystrophies

A young lady presents with a short history of progressive difficulty in walking, and now has shortness of breath. She was brought to DEM with RR 32 b/min, oxygen saturation of 90% on room air. Neurological examination reveals normal higher mental function, reduce power in all four limbs, left sided ptosis, absent DTRs, bilateral plantar responses and no sensory loss.

Q: How would you asses her clinically at this stage?

A: ability to protect, bulbar weakness, pooling of salive and ability to cough

B: evidence of shallow breathing, bilateral chest expansion, focal lung signs

C: evidence of autonomic dysfunction

D: neurological examination

Baseline bloods, ABG

get the past history, examination

In this case the most likely diagnosis is GBS

Q: What conditions may precede or trigger GBS?

A:

i. often preceded by URTI or diarrheal illness caused by various pathogens such as -CMV, EBV, HSV, mycoplasma, chlamydia, campylobacter jejuni.

ii. vaccines - rabies, swine flu

iii. pregnancy

iv. surgery

v. cancer (Hodgkin's disease)

Q: What are the indications for ICU admission?

A:

-rapid progression of symptoms

-aspiration

-bulbar dysfunction

-bilateral facial weakness

-neck weakness with inability to raise head against gravity

-significant dysautonomia

-evidence of respiratory failure

Q: what are the various monitoring parameters you would use to make a decision to intubate this lady?

• Inability to protect airway
• significant hypoxia or hypercarbia
• bedside assessment of respiratory muscle weakness, such as increased RR, decreased VT, paradoxic inward movement of abdomen during respiration, use of acessory muscles, ineffective cough
• 20-30-40 rule (Lawn et al.)

-VC <>

Glutamine and Arginine in ICU nutrition

I want to make a note on arginine and glutamine today, just for me to remember some important points if asked during viva.
Glutamine

• serves as an oxidative fuel and nucleotide precursor for enterocytes and immune cells, mainly lymphocytes, neutrophils and macrophages.
• regulates the expression of many genes related to signal transduction and to cellular metabolism and repair.
• During critical illness glutamine is released in large quantities from skeletl muscle in order to supply this need. In these circumstances it may become 'conditionally essential' and is vulnerable to depletion, with potentially adverse effects on gut barrier and immune function which may in turn impair the ability to survive a sustained period of critical illness once glutamine stores are depleted.
• Evidence is debatable. Reductions in infectious complications and length of ICU stay were shown in small early studies of enterally fed trauma and burns patients. A larger study in unselected ICU patients found no effect on any outcome. (Intensive Care Med 2003).
• The evidence for TPN is contradictary. There are suggestions from meta analysis that there is a demonstrable mortality benefit from higher doses of parenteral glutamine (http://www.criticalcarenutrition.com/). This awaits confirmation in a large RCT. It seems that the patients most likely to benefit are those requiring TPN for more 10 days.

Arginine

• a non-essential amino acid acts as a precursor of NO, polyamines (important in lymphocyte maturation) an nucleotides.
• Animal studies suggest enhanced cell mediated immunity and survival when arginine is supplemented.
• Several commercially available enteral feeding solutions combine omega 3 fatty acids, arginine, nucleotides and in one case glutamine to produce imune enhancing diets. They have been assessed in a number of trials. Meta-analysis has suggested reductions in hospital stay and infections but not in mortality.
• Subgroup analysis revealed an increase in mortality when arginine supplementation was given to septic patients (JAMA 2001). Interim safety assessment of a RCT led to its early cessation when this finding was replicated in the subgroup of patients with sepsis (Intensive Care Med 2003). It appears that arginine should not be used septic patients. There are suggestions of benefit in patients undergoing surgery or suffering from a burn injury, there is little basis for their general use in ICU patients unless it is justified by future prospective trials.

Reference: Oh Intensive care manual

Please refer to recent post for the update

Steroid for Acute Traumatic Spinal Cord Injury

This article just to help me in giving my evidence during management of traumatic SCI
Methylprednisolone is the only treatment that has been suggested in clinical trials to improve outcomes in patients with acute traumatic, nonpenetrating SCI. It has been shown that in animal studies, glucocorticoids reduces edema, prevents intracellular potassium depletion, and improves neurologic recovery.

Two blinded randomized controlled trials studied the efficacy of glucocorticoid therapy in patients with acute SCI.
1. The National Acute Spinal Cord Injury Study (NASCIS) II compared methylprednisolone (30mg/kg I.V., followed by 5.4mg/kg/hr over 23hours), Naloxone and placebo in 427 acute SCI patients. (J.Neurosurgery 1992;76(1))
At one year, there was no significant difference in neurologic function among treatment groups. However, within the subset of patients treated within eight hours, those who received methylprednisolone had a modest improvement in motor recovery compared with those who received placebo. Wound infections were somewhat more common in patients who received methylprednisolone.
2. NASCIS III compared three treatment groups: methylprednisolone administered for 48h, methylprednisolone administered for 24h, and tirilizad mesylate (a potent lipid peroxidation inhibitor) administered for 48 hours in patients with acute complete or incomplete TSCI. (J Neurosurg. 1998;89(5)). All 499 patients received an initial IV bolus of 30mg/kg methylprednisolone and were treated within 8 hours of TSCI. For patients treated between three hours, there was no difference in outcomes among treatment groups at one year. For patients treated between 3 to 8 hours, 48 hours of methylprednisolone was associated with a greater motor but no functional recovery, compared to other treatments. Patients who received the longer duration infusion of methylprednisolone had more severe sepsis and severe pneumonia compared with the shorter duration of infusion; mortality was similar in all treatment groups.

Data analysis led to the conclusion that the risk of high dose steroids outweight their benefits, and this therapy has been abandoned by many medical centres. A Consortium for Spinal Cord medicine concluded that no clinical evidence exists to definitely recommend the use of steroid therapy. (www.pva.org paralysed veterans of America)

Community Acquired Pneumonia

This week is another busy week since the third block of undergraduate medical students are starting their new session this coming Monday. I have to ensure the course guideline, log books and rosters are ready by then. I am just helping the department, yes the department (not MY department). I am having problem with someone, let me correct it not just me..at least there are two more members feel the same way......"Please" costs nothing, "Sorry" costs your pride, "I forgive you" liberates you from the shackles of prejudice.

The mortality of CAP patients admitted to ICU is about 35%. About 20% of patients admitted to ICU with CAP are in septic shock, with mortality as high as 60%.
The presence of comorbidities below contribute significantly to mortality and also alter the etiologic organisms underlying the infection.

1. COPD
2. asthma
3. diabetes mellitus
4. renal insufficiency
5. congestive heart failure
6. coronary artery disease
7. malignancy
8. alcoholism
9. age>70years
10. chronic nerological disease
11. chronic liver disease

The most common pathogens are:

1. Strep pneumonia
2. Legionella species
3. Staphylococcus aureus
4. Haemophillus Influenza
5. Gram negative bacilli

Pathogens associated with underlying comorbid condition:
1. S.pneumonia

• Dementia
• congestive heart failure
• COPD
• Cerebrovascular disease
• Institutional crowding
• seizures

2. Penicillin resistant and drug resistant pneumococcus

• age>65
• alcoholism
• immunomodulating illness or therapy (including steroids)
• Previous B lactam therapy within 3 months
• Multiple medical comorbidities
• exposure to child in day care centre

3. Enteric gram negatives

• residence in long term facility
• underlying cardiopulmonary disease
• recent antibiotic therapy
• multiple medical comorbidities

4. Pseudomonas aeruginosa

• broad spectrum antibiotics for > 7 days in the past month
• structural lung disease (bronchiectasis)
• corticosteroid therapy
• malnutrition
• undiagnosed HIV infection
• netropenia

5. Legionnaires' disease

• AIDS
• haematologic malignancy
• end stage renal disease

Non infectious diseaseas masquerading as CAP should be excluded:

1. Cryptogenic organizing pneumonia (COP)
2. Eosinophilic pneumonia
3. Hypersensitivity pneumonia
4. Drug induced pneumonitis: methotrexate, nitrofurantoin, gold, amiodarone etc
5. Pulmonary vasculitis
6. PE/ infarction
7. Pulmonary malignancy
8. Radiation pneumonitis
9. TB

The following are the major reasons for a failure to respond to anti microbial agents:

1. Wrong antibiotic: wrong spectrum or drug resistance. Wrong dosage
2. Viral, fungal, or opportunistic pathogen.
3. Unusual pathogens
4. Superadded complication
5. Complicated pleural effusion/ empyema
6. endocarditis
7. Purulent pericarditis
8. Septic arthritis
9. Meningitis
10. Exclude masquerader
11. Consider CA-MRSA in toxic patients and those with severe disease.

Unusual pathogens

1. Coxiella burnetii - cats, goats, sheep, cattle
2. Tularemia - rabbits, ticks
3. Leptospirosis -rats
4. Hantavirus - rats
5. SARS
6. Psittacosis - birds
7. Nocardia - steroids
8. Aspergillus -steroids
9. Pneumocystis jiroveci -immunosuppression
10. Dimorphic fungi -recent travel
11. Burkhodelria pseudomallei -recent travel
12. TB

Complicated Pleural effusions -
drainage is necessary if the pleural fluid is grossly purulent or if pleural fluid show the following

• pH less than 7.2
• Glucose less than 2.2mmol/l
• WCC > 10,000/ml

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