General ICM Flashcards
If a patient doesn’t respond to a fluid challenge, what does this mean?
- The patient is intravascularly full and another cause of shock should be sought
or - The patient is so hypovolaemic that not enough fluid has been given to result in a response
How can you assess whether a patient might be fluid responsive?
- Clinically - tachypnoea, tachycardia, hypotension, cool peripheries, end organ dysfunction - oliguria, confusion, arterial line swing
- Fluid challenge - 250mls fluid over 5 mins
- Straight leg raise
- CO monitoring
- ECHO - kissing ventricles, RV volume statu, IVC collapsibility/distensibility
What are the different methods of CO monitoring?
Non-invasive - ECHO, thransthoracic impedance
Minimally invasive - PICCO, LIDCO, flotrac, oesophageal doppler, TOE
Invasive - PAFC
Describe the PAFC
8 French calibre
110cm in length
Distal lumen used to measure PCWP and for sampling mixed venous blood
Proximal lumen at 30cm from tip that’s used to monitor CVP and to inject cold to measure CO by thermodilution
Thermistor 3.7cm proximal to tip
10cm long thermal filament which allows CO calculation without cold saline bolus
1.5ml balloon located at the tip
What is normal right atrium pressure?
3-8mmHg
What is normal RV pressure?
25/0-10 mmHg
What is the normal pressure in the pulmonary artery?
25/10-20 mmHg
What is the PCWP?
Trace from a branch of the PA
Similar to the CVP
4-12mmHg
Reflects left atrial pressure
What information is measured by the PAFC?
CO CVP RAP RVP PAP PCWP SvO2 Core temp
Which variables are derived from the PAFC?
CI SV SVI SVR SVRI PVR PVRI
What are mixed venous sats?
The oxygen sats of venous blood in the pulmonary arterial tree, after mixing with anatomical and physiological shunt
Exceeds the ScvO2 in healthy people as it samples from the SVC and the brain has a higher oxygen extraction ratio
In which situations might ScvO2 exceed SvO2?
- Anaesthesia
- TBI
- Shock
What are the complications associated with use of the PAFC?
CVC-related: Bleeding/haematoma, air embolism, vascular injury, arterial puncture, pneumothorax, tamponade
Floating catheter: arrythmias, tamponade, valvular trauma, misplacement, knotting
PAC in situ: VTE, pulmonary infarct, pulmonary arterial rupture
What is the evidence for PAFCs?
The PAC-man trial (2005) was an RCT that showed no difference in in-hospital mortality, ICU or 28-day mortality, or ICU of hospital LOS.
10% complication rate
No clear evidence of benefit or of harm
The authors concluded that they were most useful in undifferentiated shock, RVF and pulmonary HTN although the study was under powered for this
What is the doppler effect?
When a sound wave reflects off a moving object, the frequency shift is proportional to the velocity of the object - the basis for oesophageal doppler monitoring
How does oesophageal doppler work?
The US probe emits US waves that are reflected off RBCs travelling in the descending aorta, producing a velocity-time curve of blood flow
The stoke distance (the distance travelled by the blood in one heart beat) is then calculated
The aortic cross-sectional area is then determined from a normogram based on height and weight, and multiplied by the stroke distance to give stroke volume
Describe an oesophageal doppler probe
90cm long
Markers at 35, 40 and 45 cm to aid placement
The descending aortic doppler trace is normally obtained between 35-40cm
The probe must be directed posteriorly
What assumptions are made when using the oesophageal doppler?
- The angle of the probe to the direction of blood flow is constant
- The aortic CSA is constant throughout the cardiac cycle
- There is laminar flow within the aorta
- 70% of the cardiac output enters the descending aorta
In ODM what is the flow time corrected?
The time in milliseconds that the heart spends in systole, corrected for heart rate
A low value indicated high afterload and a low value indicates low afterload
In ODM, what is the stroke distance?
The distance that a column of blood moves along the aorta with each contraction of the LV - it’s the area under the velocity time curve - multiply by aortic CSA to get SV
In ODM, what is the mean acceleration?
The angle of the upslope
Used as a marker of LV contractility.
When should ODM be used?
Recommended by NICE perioperatively to guide fluid therapy
Studies show decreased complication rate and shorter LOS in hospital
What is delirium?
An acute change in consciousness and awareness that fluctuate with time?
What are the typical features of delirium?
- Disordered thinking
- Reduced attention
- Abnormal sleep/wake cycle
- Abnormal psychomotor activity
- Abnormal perceptions
- Abnormal emotional behaviour
What are the 4 diagnostic criterion for delirium according to the DSM IV?
a) disturbance in consciousness
b) change in cognition
c) acute
d) caused by the direct physiological consequences of a general medical condition, or drug/withdrawal induced
What is the ICD-10 definition of delirium?
a) clouding of consciousness
b) disturbance of cognition
c) psychomotor disturbances
- unpredicatble shifts from hypo to hyper activity
- increased reaction time
- increased or decreased speech
- enhanced startle reaction
d) sleep/wake disturbance
e) acute
f) underlying illness is responsible
What is the pathophysiology of delirium?
Neurotransmitter imbalance, with reduced acetylcholine and increased dopamine resulting in neuronal excitability
There may also be cerebral microvascular dysfunction following exposure to inflammatory mediators, or global failure of oxidative metabolism resulting in cerebral insufficiency
How common is delirium?
Very
70-80% of mechanically ventilated patients are affected
What are the subtypes of delirium?
- Hyeractive - confused, agitated, combative, aggressive, paranoid - 1%
- Hypoactive delirium - inattentive, stuporous, withdrawn, often mistaken for depression - 35%
- Mixed - 64%
What are the risk factors for the development of delirium?
- Patient factors
- age, comorbidities, baseline cognitive impairment, psychiatric history, alcohol or substance abuse - Illness related
- high APACHE II score, sepsis, hypoxaemia, metabolic derrangement, surgery esp CPB - Iatrogenic
- disturbed sleep/wake cycle, sedatives esp benzos, anticholinergic medication
What are the adverse consequences of delirium?
- Increased risk of short-term complications e.g. accidental extubation/line removal
- Medium term complications - increased LOS, increased duration MV, increased mortality (independent risk-factor for a 3-fold increase in mortality at 90 days)
- Long-term complications - risk of PTSD, risk of long-term cognitive impairments
How is delirium diagnosed on the ICU?
The 2 most widely used bedside scoring systems are
- Confusion assessment method (CAM) - ICU
- Intensive Care Delirium Screening Checklist (ICDSC)
Describe CAM-ICU
- Is the patient different from their baseline mental status? or has the patient had any fluctuaiton in mental status in the past 24 hours?
- Test of inattention - hand squeezing on the letter A >2 = positive
- Is the RASS score anything other than 0
- Disorganised thinking - e.g. will a stone float on water
Feature 1 plus 2 and either 3 or 4 present = CAM-ICU positive
What can be done to reduce the risk of delirium?
The ABCDE bundle (Vasilevskis et al 2010)
Awake and Breathing (daily sedation breaks and SBTs)
Choice of sedation - minimise medications that can provoke delirium e.g. benzos
Delirium monitoring
Early mobilisation
Plus, sleep hygiene, removal of invasive lines when no longer needed
What is the pharmacological management of delirium?
- Antipsychotics are the drug of choice for those posing risk to themselves e.g. haloperidol, olanzipine
- Use of dexmedetomadine as a sedation agent
What trials support use of dexmedetomidine for management of delirium?
- DahLIA trial (JAMA 2016) - double blind MC RCT. Showed a statistically significant reduction in median ventilator-free hours at day 7 and a significant decrease in antipsychotic use. Non-significant decrease in ICU LOS.
- Midex-Prodex trial (JAMA 2012) - DB MC parallel design that showed the non-inferiority of dexdor when compared to midaz or propofol. Duration of sedaiton was significantly shorter with dexdor. There was a non-significant decrease in ICU LOS.
What is drowning?
Primary respiratory impairment following submersion or immersion in a liquid medium, whatever the outcome.
The term near drowning is no longer used.
How id drowning classified?
According to the findings at the scene
- No evidence of aspiration
- Evidence of aspiration but with adequate ventilation
- Evidence of aspiration with inadequate ventilation.
- Absent ventilation and drowning
What cardiovascular pathophysiological changes occur as a result of drowning?
- The diving reflex. Stimulated by cold water to the face. Mediated via CN V1. Results in apnoea, bradycardia and vasoconstriction
- A massive cathecholamine surge during the diving reflex causing profound vasoconstriction, arrhythmias, pumonary oedem.
- Progressive hypoxaemia and hypothermia leading to bradycardia, pulmonary hypertension and cardiac failure
What neurological pathophysiological changes occur as a result of drowning?
Hypoxic brain injury
- starts within 5 minutes
- hypothermia not usually protective because its onset is unlikely to occur before the hypoxia starts
What are the metabolic consequences of drowning?
Hypothermia
No clinically significant differences in volume status, electrolytes or lung function in those who drown in fresh compared with salt water
What are the infective consequences of drowning?
Aspiration of contaminated fluid results in infection in up to 50%
Aerobic gram positive organisms (strep/staph) may be aspirated from the oropharynx
Aerobic Gram-negative organisms (e.g. Pseudomonas, Aeromonas, Burkholderia pseudomallei, Leptospira) may contaminate fresh water
Fungal infections including delayed CNS infections due to Aspergillus and Pseudallescheria boydii are a risk, esp in immunocompromised patients.
Describe the pathophysiology of drowning
Immersion or submersion results in panic, breath-holding, laryngospam, aspiration and swallowing of water. These lead to hypoxia, which eventually results in relaxation of laryngeal muscles. Hypercapnia and acidosis result in respiratory stimulation which result in aspiration. This results in direct alveolar toxicity - resulting in pulmonary oedema, surfactant washout and dysfunction resulting in atelectasis and bronchospasm.These all result in V/Q mismatch (shunt), reduced compliance and ARDS.
What are the risk factors for drowning?
- Age - 0-4 year olds may drown in the bath tub, or swimming pools e.g where fencing is inadequate. Adolescence when risk taking behaviour may occur.
- Male gender
- Intoxication
- Occupation/hobbies - scuba diving, farming, fishing
- Medical conditions - IHD, cardiomyopathies, arrhythmias, epilepsy, diabetes, depression
- Conditions increasing the risk of drowning - currents, rip tides, waves, cold water.
What is the immediate management of a drowning victim at scene?
- Remove from the water
- Consider whether spinal precautions are needed
- 5 rescue breaths
- Start chest compressions if there’s no response
- Compression only CPR is not appropriate in drowning
- Consider the effects of hypothermia
What is the immediate management of a drowning victim on arrival to hospital?
- ATLS approach - secure airway is needed, treat any life-threatening injuries
- Optimize oxygenation - lung protective ventilation, bronchoscopy may help to remove the aspirated debris
- Optimize cardiac output - fluid resus as likely to be hypovolaemic, may need vasopressors/inotropes
- Neuroprotective measures
- Temperature control
Is there any evidence for the use of ECMO in drowning?
A retrospective review published in Resuscitation 2016 (Burke et al) revealed 247 patients who received ECLS following drowning between 1986 and 2015. Cardiac arrest with ROSC prior to ECLS occurred in 34.8%, ECLS was initiated during cardiac arrest in 31.2% and 34% did not arrest prior to ECLS. Overall survival was 51.4%, with al increase in survival across all 3 categories. Veno-venous ECLS was associated with a better survival that veno-arterial ECLS in patients with cardiopulmonary failure. The presence of AKI and need for CPR during ECLS were associated with increased mortality.
What are the indicators for a poor prognosis in drowning victims?
- Submersion > 5-10 minutes
- Resuscitation not attempted for > 10 minutes after resuce
- > 25 minutes of resuscitation
- GCS < 5 or unreactive pupils on arrival to hospital
- Pulseless and apnoeic on arrival to hospital
- pH < 7.10 on initial blood gas
What determines stroke volume?
- Preload
- Afterload and SVR
- Myocardial contractility
What does preload depend on?
Ventricular end-diastolic volume (EDV), which is governed by the volume and pressure of blood returning to the heart.
Haemorrhage, sepsis, anaphylaxis and raised intra-thoracic pressure are all common causes of inadequate preload.
What increased afterload?
Valve stenosis, hypertension, high SVR, low intrathoracic pressures and ventricular dilatation
What are the two types of failure of myocardial contractility?
- Systolic dysfunction
2. Diastolic dysfunction
Describe systolic dysfunction
- Inadequate systolic ejection which is a result of reduced contractility (e.g. ischaemia, cardiomyopathy) or increased impedence (e.g. hypertension, aortic stenosis). Increasing EDV will maintain SV provided myocardial reserve is adequate, otherwise SV and CO will fall and inotropes will be required.
Describe diastolic dysfunction
Characterised by reduced ventricular compliance with impaired diastolic filling (i.e. stiff ventricle). It may be caused by mechanical factors e.g. restrictive cardiomyopathy, or impaired relaxation due to myocardial ischaemia or severe sepsis.
- The resulting increase in end-diastolic pressure and associate venous congestion can cause characteristic ‘flash’ pulmonary oedema
Why are diabetics at increased risk of diastolic dysfucntion?
Endomyocardial ischaemia caused by small vessel arteriopathy
Why are renal failure patients at increased risk of diastolic dysfunction?
Hypertension - blood flow from the epicardium to endomyocardium is impeded by ventricular wall hypertrophy and the resulting ischaemia impairs ventricular relaxation
What are the ethical principles that govern management of donation after cardiac death prior to withdrawal of life-sustaining support?
- No treatment aimed at organ donation should be started prior to the decision to withdraw being made.
- Maintenance of life-sustaining treatment can be considered in the best interests of patients who wanted to be donors if this facilitates donation and doesn’t cause harm or distress.
- Agents can be used to maintain arterial pressure
- It’s not appropriate to initiate treatment against the wishes of the family
What is the process of OD after circulatory death?
- Withdrawal of life-sustaining treatment one retrieval team and family are ready.
- Following cessation of cardio-resp function there is a 5 minute window to confirm monitored asystole prior to certification
- The relatives have 5 minutes to spend with the patient prior to transfer to the OT
- For lung donation reintubation is required and lungs are recruited with a single breath and CPAP maintained with 100% O2. Ventilation is reinstated once the chest has been opened and the aorta clamped.
What is functional warm ischaemia?
Starts when the SBP falls below 50mmHg of sats < 100%. Stand-down times from the onset of FWI vary by organ and by receiving centre. Approx times are:
- Liver 30 mins
- Pancreas 30 mins
- Lungs 60 mins from FWI to reinflation
- Kidney 120 mins
What is the Maastricht classification of donation after cardiac death
There are 2 principle types of DCD - controlled and uncontrolled
1 - uncontrolled - dead on arrival
2 - uncontrolled - unsuccessful resus
3 - controlled - cardiac arrest following planned withdrawal
4 - either - cardiac arrest in a patient who is drain dead
5 - uncontrolled - cardiac arrest in hospital inpatient
What are the absolute contra-indications to organ donation?
Absolute:
vCJD
HIV disease
Unlikley to be accepted:
- Active invasive cancer in the past 3 years excl non-melanoma skin cancer and primary brain tumour
- Primary intracerebral lymphoma
- All secondary intracerebral tumours
- Haematological malignancy
- Melanoma
- Untreated systemic infection
- Active and untreated TB
- West Nile virus
- History of Ebola infection
There is no upper or lower age limit
What are the main disorders of consciousness?
- Coma
- Vegative state
- Minimally conscious state
What is a coma?
- A state of absent wakefulness and absent awareness
- Unrousable unresponsiveness lasting > 6 hours
- Can’t be awakened
- Fails to respond to pain, light and sound
- Lacks normal sleep-wake cycle and
- Does not initiate voluntary actions
What is a vegatative state?
- Wakefulness with absent awareness
- Severe cortical damage with preservation of some brainstem activity
- Preserved capacity for spontaneous or stimulus-induced arousal, evidenced by sleep-wake cycles and a range of reflexive and spontaneous behaviours
- Complete absence of environmental awareness or awareness of self
What is a minimally conscious state?
- Wakefulness with minimal awareness
- A state of severely altered consciousness in which minimal but clearly discernible behavioural evidence of self or environmental awareness is demonstrated.
- Inconsistent by reproducible responses above the level of spontaneous or reflexive behaviour.
What are the causes of disordered consciousness?
- TBI
- Vascular event - ICH, SAH, CVA
- Toxic/metabolic - alcohol, drugs/poisons, anaesthetics, benzos, hypoglycaemia, hyper or hypo-osmolar states
- Infection - encephalitis, abscess, vasculitis, sepsis
- Hypoxia
- Systemic illness - liver failure, renal failure, endocrine
How would you manage a patient presenting with disordered consciousness?
ABCDE approach
Intubation to protect the airway if GCS < 9
Indentify cause - BM, u+es, LFTs, ammonia, FBC, TFTs, ABG, culture, CT/MRI, consider LP
Maintain normal physiology - o2, BP, correct hypoglycaemia, correct hypo/hyperthermia, correct electrolyte abnormlities
Review meds
EEG
Detailed neurological assessment
ICP management if needed
How can you prognosticate in hypoxic brain injury following cardiac arrest?
- Should start 72 hours after ROSC
- Exclude confounders
- If M1-2 and no pupil or corneal reflexes or bilateral absent SSEPs ->poor outcome very likely (FPR < 5%, 95% CI)
- If these criteria aren’t met them two or more of the following also suggest likely poor outcome
- status myoclonus < 48 hours after ROSC; High NSE level, Unreactive birst-suppression or status on EEG, diffuse anoxic brain injury on CT.
What EEG features suggest poor outcome following cardiac arrest?
- Absence of EEG reactivity to external stimuli
- Presence of burst suppression
- Status epilepticus
What is locked in syndrome?
Results from brain stem pathology that disrupts voluntary control of movement
Wakefulness and Awareness are both still preserved
Able to communicate by blinking
What is sepsis?
A life-threatening organ dysfunction caused by a disregulated host response to infection
(SEPSIS-3 definition, published in JAMA 2016)
What is septic shock?
A subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality that with sepsis alone
- Identified clinically by vasopressor requirement, or lactate > 2
- The combination is associated with an in-hospital mortality of > 40%
What is the qSOFA score?
Used as a quick bed-side guide to diagnosing those with poor outcomes due to sepsis, if they have 2 or more of the following
- RR > 21
- SBP < 100
- GCS < 15
What is the pathophysiology of sepsis?
- Vasoldilatation (iNOS causes endothelial NO production)
- Loss of endothelial integrity due to inflammatory mediator-related disruption of the tight junctions
- Reduced cardiac contractility
- Activation of the coagulation cascade and fibrinolysis due to IL-1,6 and TNF-a
- Mitochondrial dysfucntion - results in reduced O2 utilisation
What are exotoxins?
Peptides secreted by Gram +ve bacteria
What are endotoxins?
Located within the Gram -ve bacterial cell walls
How should sepsis be manages?
- Measure lactate, Obtain cultures, administer broad-spectrum antibotics
- 30mls/kg IV fluid for hypotension/ lactate > 4
- if hypotension persists then vasopressors to maintain MAP > 65 and reassess fluid status e.g. CVP, ScvO2, ECHO, SLR, LiDCO
What is brain death?
A complete and irreversible loss of brain and brainstem function as a result of neurological injury. The heart is still beating but respuratory function is dependent on a ventilator.
The Academy of the Medical Royal Colleges Uk outlines 3 essential components
-1. Fulfilment of essential preconditions
-2. Exclusion of potentially reversible causes of coma
-3. Formal demonstration of coma and apnoea.
What are the preconditions for brainstem testing?
- Pt should be deeply unconscious, apneoic and mechanically ventilated
- Irreversible brain damage of known aetiology
What are the exclusion criteria for brainstem testing?
Ensure that coma is not secondary to reversible factors such as CNS depressant drugs, biochemical/metabolic abnormalities or hypothermia.
What approaches are there that can help exclude drug intoxication being the cause of a coma?
- A period of observation 2-3 times the elimination half-life of the drug in question
- Administration of specific antagonists
- Plasma analysis
- Confirmatory test to confirm absence of cerebral flow/perfusion
What are the potentially reversible causes for coma?
- Circulatory - ensure MAP > 60
- Respiratory - ensure normal pH, PCO2< 6, PO2 > 10
- Metabolic - ensure temp > 34
- Biochemical - ensure Na 115-160, K > 2, Mg 0.5-3, Po4 > 0.5, gluc 3-20
Which agents can you carry out a plasma analysis on to ensure that they are not the cause of a coma?
- Midazolam - brainstem testing should not take place if levels > 10 micrograms/litre
- Thiopentone - brainstem testing should not be done if levels > 5 mg/l
Who can perform brainstem death testing?
2 competent clinicians who have held GMC registration for > 5 years, one of whom must be a consultant
What does brainstem testing test for?
- It assesses the integrity of the sensory and motor pathways of the cranial nerves reflexes
- An apnoea test.
Describe the assessment of the cranial nerves in brainstem testing
- Pupillary reflex (afferent II, efferent III) - check for direct and consensual reflexes
- Corneal reflex (afferent V, efferent VII) - the cornea os brushed lightly with a swab
- Response to painful stimuli (Afferent V, efferent VII) - a painful stimulus is applied to the supraorbital ridge
- Vestibulo-ocular reflex (afferent VIII, Efferent III, IV, VI)- visualise the TM prior to beginning the test. Instil 50mls ice cold saline into each external auditory meatus in tuen, looking for eye movements/nystagmus
- Gag reflex (afferent IX, efferent, X) - the pharynx is stimulated with a spatula/similar
- Cough reflex (afferent X, efferent X) - a bronchial catheter is passed down the ET tube to stimulate the carina
How do you carry out the apnoea test for brainstem testing?
- Increase FiO2 to 1.0
- Perform ABG to confirm measured PaCO2 and SaO2 correlate with monitored values
- decrease the MV until ETCO2 > 6. Check PaCO2 > 6 and pH < 7.4 on ABD
- Maintain apnoeic oxygenation by either instilling 5L O2 per minute via suction catheter of by using CPAP
- Five minute observation to look for the presence of spontaneous resp activity
- Perform final ABG to confirm an increase in PaCO2 of > 0.5kPa
Following the test the ventilator should be recorrected and any acid-base abnormality corrected prior to carrying out the second set of tests. There is no defined time period between the 2 sets.
When is legal time of death?
The time at which the first set of tests was completed
In which circumstances might you not be able to confirm brainstem death via clinical tests alone?
- Inability to exclude the influence of sedatives
- High cervical cord injury
- severe maxillofacial injury
What auxiliary tests can be carried out to establish brainstem death where clinical testing alone cannot be used?
- Measure brain electrical activity
- EEG - little value in hypothermia or drug intoxication as these factors suppress neuronal activity
- SSEPS - peripheral stimulus to median nerve looking for response at the contralateral primary sensory cortex - Flow studies
- cerebral angiography - reveals absence of intracerebral filling beyond the entry of the carotid and vertebral arteries into the skull
- transcranial doppler - useful only if a reliable waveform is found - complete absence of flow may not be reliable if inadequate windows exist
Why might patients with haematological malignancy require critical care admission?
- Neutropenia and sepsis
- Resp failure - infection, pulmonary oedema/haemorrhage/infiltration by underlying disease
- Tumour lysis syndrome
- Graft vs host disease
- Complications of chemotherapy and stem cell transplant
- CNS dysfunction and seizures - hyperviscosity syndrome/intracerebral bleed or thrombosis, underlying malignancy, electrolyte imbalance
- GI dysfunction including neutropenic enterocolitis (typhlitis)
- Acute renal failure - nephrotoxic drugs/sepsis/underlying disease
How does NICE define neutropenia?
Neutrophil count < 0.5 x 10(9)/l
How does NICE define neutropenic sepsis?
Neutropenia and clinical signs of infection OR temp > 37.9
What precautions should be taken when looking after a neutropenic patient to reduce risk of sepsis?
- Reverse barrier nursing
- Positive pressure side room isolation
- Avoid invasive procedures where possible
- Avoid rectal exam/rectal temp probe insertion
- Meticulous oral hygiene
What are the principles of management for a patient with neutropenic sepsis?
ABCDE aproach
- History and exam - including pets/exposure/hobbies/travel/occupation/invasive lines. Examine for infection ensuring you check oropharynx, skin and perirectal areas.
- Follow surviving sepsis guidelines - cultures, antibiotics, lactate, bloods, fluid and vasopressors as needed
- Imaging - CXR and any abdo imaging as necessary
What should an antibiotic regime for neutropenic sepsis include?
- IV anti-pseudomonal B-lactam e.g. piperacillin-tazobactam or meropenem
- Additional antibiotics (e.g. aminoglycoside) if Gram-negative or resistant organisms suspectd, or if hypotensive or potential respiratory infection
For those anaphylactic to penicillin alternatives include ciprofloxacin and clindamycin, or vancomycin and aztreonam
What is tumour lysis syndrome?
Metabolic derangement that occurs when large volume tumour cells are lysed, usually following chemotherapy. Typically a/w acute leukaemia and high-grade lymphomas
Metabolic derangement include hyperkalaemia, metabolic acidosis and renal failure, severe hypocalcaemia and hyperphosphataemia can occur and increased serum and urinary urate levels are seen
What is the treatment of tumour lysis syndrome?
ABCDE approach
- Aggressive fluid resuscitation
- Treat hyperkalaemia
- Rasburicase (a recombinant urate oxidase enzyme which reduces plasma uric acid concentration)
What complications of a stem cell transplant may result in ICU admission?
Early (< 100days)
-infection, haemorrhage, acute GvHD, interstitial pneumonitis, aplastic anaemia secondary to graft failure
Late complications
-chronic GvHD, chronic pulmonary disease, infections, autoimmune disorders
What is host vs graft disease?
An immune-mediated disease following allogenic haematopoietic cell transplant (and transplant of solid organs containing lymphoid tissue) that results from a complex interaction between donor and recipient adaptive immunity (APCs of the recipient interact with the mature T-cells of the donor). It can occur even when the donor is perfectly matched
How does acute host vs graft disease present
Typically with enteritis, hepatitis and dermatitis
Diagnosis can be histological (skin, liver, rectal) or by using a clinical diagnosis and staging system
How does chronic GvHD present?
Diverse syndrome with varying clinical features resembling autoimmune disease e.g. sclerodermia, primary biliary cirrhosis, bronchiolitis obliterans and chronic immunodeficiency.
What are the treatment options for GvHD?
- High dose steroids
- Immunosuppressant e.g. ciclosporin
- Parenteral nutrition may be required to facilitate gut rest
What is typhlitis?
Neutropenic enterocolitis
Life-threatening complication of chemotherapy
Symptoms include nausea, abdo pain and distension, fever and chills
Poor prognosis and successful treatment depends on an early diagnosis achieved with a high index of suspicion and use of CT imaging. Elective right hemicolectomy may be required to prevent recurrence.
What are the aims of fluid resuscitation?
- Replace normal fluid and electrolyte losses
- Maintain BP, cardiac output and tissue perfusion to satisfy metabolic needs, aid temperature regulation and facilitate waste removal
- Replenish substantial defects or ongoing losses
- Avoid excessive tissue oedema
What is compartmental distribution of water dependent on?
- Osmotic pressure exerted by small diffusible ions e.g. Na
- Osmotic pressure reflects ion concentration gradients between compartments created by cellular ion pumps, e.g. Na and Cl that are mainly extracellular and K and PO4 that are intracellular
e. g. saline increased extracellular Na and Cl, raising ECF osmotic pressure and attracting water out of the intracellular compartments in to the ECF
What does intravascular volume depend on?
- Plasma oncotic pressure - which is the ability of large plasma proteins to bind and retain water in the circulation. POP is normally ~ 3.4kPa with 75% of the effect due to albumin, 20% Hb and 5% globulins. 1g albumin ‘binds’ about 18mls water, thus intravascular albumin binds ~ 2.25L of plasma water
- Vascular permeability - normal albumin leakage across capillary membranes is limited to 4-5% per hour by its high MW and negative charge. Thus all of the normal intravascular albumin leaks into the ISF each day. It returns via the lymph and thoracic ducts at the same rate. Inflammation increases vascular permeability and albumin leakage by up to 300%. Acute illness also decreases production of albumin by 15g/day. Low albumin reduces intravascular volume, and increases in ISF albumin causes oedema
- Circulatory hydrostatic pressure - increases leakage of intravascular water, whilst plasma oncotic pressure draws water into and maintains plasma volume
What is the normal daily water requirement?
1.5-2.5L /day
What is the normal Na requirement /day?
~70-100mmol
1-1.5mmol/kg/day
What are the normal K requirements/day?
40-70mmol/day
0.5-1mmol/kg/day
What is normal urine osmolality?
620-740 mosmol/dau
What is the compartmental breakdown of fluid?
60% of body weight
~42L in a 70kg man
~25L = IC and 15-17L = EC
The ECF comprises ISF 11-13L and intravascular plasma 3-4L
What is HUS?
Haemolytic uraemic sydrome It's a triad of 1. Microangiopathic haemolytic anaemia 2. Thrombocytopenia 3. Renal failure
What causes HUS?
There are 2 causes - epidemic and atypical. The epidemic form is a/w a prodromal illness and bloody diarrhoea following infection with verotoxin-producing enterococci (E.coli 0157) or Shigella
Atypical is much rarer and has a poorer prognosis. It may occur following
-step pneumoniae, CMV or HIV infection
-bone marrow transplant/solid organ transplantation
-drug exposure e.g. quinine, heroin, ciclosporin
-malignancy
-pregnancy
What is the pathophysiology of HUS?
Following ingestion of the toxin bloody diarrhoea occurs as a result of haemorrhagic colitis. AKI develops as a result of direct injury to the renal vascular endothelium secondary to toxin production. This leads to excessive platelet aggregation, platelet microvascular thrombin and ultimately AKI. Subsequent HTN and fluid overload are common
-In atypical HUS there is often dysregulation of the complement system
What investigations would you carry out in someone suspected of having HUS?
- Bloods
- FBC and film: looking for reticulocytes, evidence of haemolysis and thrombocytopenia
- Direct Comb’s test: differentiate between immune and non-immune mediated
- Lactate dehydrogenase (LDH, raised in haemolysis)
- U+Es (AKI)
- LFTs: including split bilirubin
- Clotting- incl fibrinogen and d dimers
- HIV and hepatitis serology
- Full renal screen: autoimmune and vasculitis screen - Stool MC+S
- Urinalysis
- Consider renal imaging to rule out other causes of AKI
How would you manage a patient with HUS?
ABCDE aproach Specific: 1. O2 2. Fluid and electrolyte balance 3. CV support/BP control 4. Renal and haematology input early 5. Treat the cause - cipro for e.coli and shigella 6. Plasma exchange - PEx is often used as HUS can be difficult to distinguish from thrombotic thrombocytopenia purpura initially, recommended in atypical HUS. In epidemic HUS PEx, IVIg, steroids and anti platelets have not proved beneficial
What is the prognosis in HUS?
Mortality rate is 3-5%
70-85% with epidemic HUS recover normal renal function
Atypical HUS has poorer prognosis with an initial mortality of ~25%, and up to 50% progressing to ESRD.
How does HUS differ clinically from TTP?
They are considered a spectrum of the same disease process
TTP is a malignant condition with a mortality of >90% if untreated
It’s a clinical diagnosis characterised by:
1. Thrombocytopenia
2. MAHA (microangiopathic haemolytic anaemia)
3. Fluctuating neurological signs (due to endothelial injury in the cerebral circulation)
4. Renal impairment
5. Fever
Clotting is usually normal - DIC is a late, ominous sign.
What is the underlying pathology in TTP?
The hallmark in TTP is deficiency of von Willebrand factor-cleaving protease, which may be genetic or acquired.
vWF is a large glycoprotein present in the plasma whose functions include binding factor VIII, and activating and binding platelets in response to endothelial injury. It is produced in the endothelium as ultra-large multimers that are inactivated when cleaved by the vWF-CP. In TTP, these multimers are not cleaved and there is uncontrolled platelet activation. Fibrin is deposited and thrombus propogated creating ischaemia distally, and red cells are shredded as they pass the fibrin/platelet mesh (i.e MAHA)
How is TTP managed?
Specific interventions are recommended by the British Committee for Standards in Haematology
- PEx using Octaplas, this should continue daily for at least 2 days after platelet counts recover. This removes the autoantibodies from the circulation and replaces their plasma with plasma containing normal levels of vWF-CP
- Adjuvant high-dose pulsed methylprednisolone can be considered. Has been shown to improve outcome but not RCT of PEx and steroids vs Pex alone
- Rituximab - used in life-threatening TTP and in patients with refractory or relapsing disease
- Low dose aspirin when plts > 50
- Supportive measures - RBC and folate supplementation during active haemolysis, plt transfusions are contraindicated unless life-threatening haemorrhage, routine thromboprophylaxis once plts > 50.
What is normal serum sodium?
135-145 mmol/l
What is total body sodium?
60mmol/kg
Where is Na absorbed?
Small intestine
In the kidney, what influences sodium reabsorption?
- Renin-angiotensin-aldosterone system
- ADH
- Thirst
- B-adrenoreceptor stimulation at the PCT
In the kidney which parts reabsorb which %s of sodium?
70% PCT
20% thick ascending loop of Henle
5% DCT
3% collecting duct
How do you classify hyponatraemia?
Typically classified according to the tonicity of the extracellular fluid/plasma osmolality and the patients volume status - specifically hyper-, eu- and hypovolaemia
What is true hyponatraemia?
Low sodium level in the presence of hypoosmolality
Hyponatraemia occurring without hypoosmolality is referred to as pseudohyponatraemia (occurs secondary to elevated levels of lipids or proteins)
Describe hypovolaemic hyponatraemia
TBW and total body sodium are low, but there is a disproportionate loss of sodium compared to water. e.g. increased ADH secretion in hypovolvaemic states (vomiting, diarrhoea, xs sweating).
Urinary sodium differentiates renal vs extra-renal losses: urinary sodium < 20 suggests an extra renal cause
Describe euvolaemic hyponatraemia
The most common category of low sodium in hospital patients. Causes include:
SIADH, glucocorticoid deficiency, hypothyroidism, low solute intake (e.g. beer potomania), psychogenic polydipsia.
describe hypervolaemic hyponatraemia
Essentially due to dilutional hyponatraemia. Oedema is seen as a result of impairment of the kidneys ability to excrete water maximally. There is paradoxical increase in total body sodium, but a simultaneous and proportionally larger increase in total body water.
Causes include:
Nephrotic syndrome, CCF, cirrhotic liver disease
What is the pathophysiology of the neurological signs seem in hyponatraemia?
Result from changes in the osmotic gradient that develops between the intracellular and extracellular fluid compartments producing tissue oedema. The effects of this tissue swelling are clinically most pronounced in the brain, where the non-compliant skull combined with lack of adaptive mechanisms means raised ICP can be rapidly devastating. This is particularly important in patients with severe hyponatraemia that has occurred over hours, when convulsions, coma and death secondary to cerebral herniation can result.
If you have low sodium and a plasma osmolality that is high (>295) what are the potential causes?
Due to shifts of water out of cells due to osmotic gradient
e.g. due to:
Hyperglycaemia
Mannitol
If you have a normal osmolality but low sodium what is the cause?
Pseudohyponatraemia - increase in the non-water component of plasma results in a falsely low reading e.g. hyperlipidaemia, hyperproteinaemia
If you have a low serum osmolality (<285), are hypovolaemic and have a low urinary sodium (<20) what are the possible causes of hyponatraemia?
Vomiting, diarrhoea, sweating, burns, pancreatitis
If you have a low serum osmolality (<285), are hypovolaemic and have a high urinary sodium (>20) what are the possible causes of hyponatraemia?
Diuretics
If you have a low serum osmolality (<285), are euvolaemic and have a low urinary sodium (<20) what are the possible causes of hyponatraemia?
Low solute intake
Polydipsia
If you have a low serum osmolality (<285), are euvolaemic and have a high urinary sodium (>20) what are the possible causes of hyponatraemia?
Hypothyroidism
Adrenal insufficiency
SIADH
If you have a low serum osmolality (<285), are hypervolaemic and have a low urinary sodium (<20) what are the possible causes of hyponatraemia?
CCF
Nephrotic syndrome
Cirrhosis
If you have a low serum osmolality (<285), are hypervolaemic and have a high urinary sodium (<20) what are the possible causes of hyponatraemia?
Renal failure
How would you manage a severely hyponatraemic patient presenting with seizures?
ABCDE approach
3% hypertonic saline until symptoms subside
The aim is to address the cerebral oedema but not to normalise sodium. Increasing the Na by 4-6 mmol/l or a level of about 120 is normally sufficient to reverse the most severe manifestations of acute hyponatraemia.
It is possible to calculate the expected change in sodium concentration on the basis of the volume of and rate at which the hypertonic saline is infused
Admit to critical care and monitor sodium levels 1-2 hourly.
The rate of increase shouldn’t exceed 8-10 mmol/l in a 24hour period.
What is central pontine myelinolysis?
Rare neurological disorder characterised by symmetrical midline demyelination of the central pons. Extrapontine lesions can occur in the basal ganglia, internal capsule, lateral geniculate body and cortex. Symptoms include motor dysfunction, respiratory paralysis, mental state changes and coma.
Osmotic demyelination is the major risk associated with excessively rapid sodium correction.
Who is at high risk of central pontine myelinolysis?
Malnourished Alcoholics Burns victims Hypokalaemia Na change > 12 mmol/24 hours.
What is SIADH?
Failure to suppress ADH production in lowered osmolality states
This results in disproportionate water retention compared with sodium.
What are the causes of SIADH?
Drugs: hypoglycaemic agents, antipsychotics, antidepressants, chemo esp vincristine and cyclophosphamide
Malignancy: Lung (esp small cell), brain, neck, duodemun, pancreas
CNS disorders: Infection, trauma, ischaemia, haemorrhage
Pulmonary disorders: Pneumonia, acute respiratory failure
Pain: Can mediate an increase in ADH secretion post-op
How do you treat SIADH?
- Fluid restrict aiming for slow rise in Na of 1-1.5 mmol/l/day
- If symptomatic - hypertonic saline 1.8%
- Demeclocycline 600-1200mg/day to inhibit the renal response to ADH (i.e it induces nephrogenic DI)
- ADH receptor antagonists are available e.g. conivaptan
Define ICU-acquired weakness
Clinically detectable weakness in critically ill patients in whom there is no plausible aetiology other than critical weakness
The underlying pathology may be myopathy, neuropathy or a mixture of both. The clinical presentations of each are indistinguishable
What are the risk factors for ICU-acquired weakness?
- Severe sepsis and MOF
- Prolonged MV
- Excessive sedation
- Muscle immobilisation
- Use of corticosteroids
- Neuromuscular blockade
- Hyperglycaemia
How is muscle weakness assessed?
Symmetrical, flaccid tetraparesis with sparing of the facial muscles
Motor weakness can be assessed using the MRC sumscore. Three muscles in both upper and both lower limbs are assessed and each graded from 0-5. A sum-scors of < 48 suggests polyneuromyopathy.
Which movements are tested in the MRC sum-score for ICUAW?
Arm abduction Flexion at elbow Wrist extension Hip flexion Extension at the knee Foot dorsiflexion
What is the differential diagnosis of ICU-acquired weakness?
- Guillain-Barre syndrome
- Myasthenia gravis
- Lambert-Eaton syndrome
- Motor neurone disease
- Spinal cord injury
- Rhabdomyolysis
- Drug-induced weakness
- Myopathy/myositis
- Infective causes, including botulism
How is ICUAW investigated?
- Lab tests: infl markers, ESR, electrolytes, CK, auto-antibodies, B12 level; LP
- Imaging - MRI brainstem and spine
- Neurophysiological investigations - Nerve conduction studies. CIM: normal; CIPN decreased compound muscle action potential and sensory action potentials with noraml conduction velocity. Electromyography: pts need to be fully compliant. Typical patterns of myopathic EMGs are motor unit potentials with small amplitudes and short duration.
- Muscle biopsy - only indicated where there is diagnositic uncertainty. Excludes other diagnoses. Allows subclassification into the 3 morphological subtypes 1. unspecific and uncomplicated CIM; 2 thick filament myopathy; 3 acute necrotising myopathy
How is ICUAW managed?
MDT supportive approach
Focus on prevention and avoidance of risk factors
Early mobilisation, sedation weaning protocols, daily physical and occupaitonal therapy
Optimise nutrition, correct electrolytes
Minimise steroids and neuromuscular blockade
Strict glycaemic control is the only strategy that has been shown to reduce the incidence of critical illness polyneuropathy - although this is in conflict with the conclusions drawn from the NICE-SUGAR trial.
What is HIV?
A cytopathic retrovirus that preferentially infects CD4-receptor positive (CD4+) T helper cells
This results in reduced immune surveillance and increased susceptibility to opportunistic infections and malignancy
What is AIDS?
Acquired immunodeficiency syndrome (now call HIV-related disease) is defined as a CD4 count < 200cells/mm3 in a person infected with HIV, or the presence of an AIDS defining illness
How is HIV classified?
According to the CDC:
Group 1 - acute seroconversion illness - occurs soon after infection, although most patients are asymptomatic. There is a high viral load, but there is a 3 months period where anti-HIV IgG antibodies are not detectable in the blood
Group 2- Asymptomatic infection - most people with HIV remain asymptomatic, the virus reproduces at a slow rate. Approx 10% will develop AIDS within the first 3 years, the remainder progress with a median of 10 years
Group 3- persistent generalised lymphadenopthy
Group 4 - Symptomatic HIV infection. Untreated patients with AIDS typically survive 3 years.
How do patients with HIV present to critical care?
- Resp failure - Pneumocystis jirovecii penumonia (PCP); exacerbations of chronic lung disease; bacterial pneumonia
- TB
- Cardiovascular disease - IHD is common - which may be attributable to HAART; endocarditis and myocarditis esp in IVDUs
- Liver failure - often due to coninfection with hep b or c. NrTIs and NNRTIs may cause hepatotoxicity
- Gastro - CMV colitis and cryptosporidial diarrhoea; GI bleeding secondary to ulcer,lymphoma or kaposis sarcoma; AIDs cholangiopathy; pancretitis
- Renal failure - HIV-associated nephropathy; diabetes and hypertension are common
- Neuro - meningoencephalitis, SOL incl toxoplasmosis, aspergillomas, abscesses or lymphoma; progressive multifocal leucoencephalopathy
What is the prognosis of patients with HIV admitted to ICU?
A poor prognosis is a/w
- high apache 2 score
- organ failure
- AIDS - defining illness
- sepsis
What is PCP?
Pneumocystis pneumonia is caused by the yeast-like fungus Pneumocystis jirovecci
It has a slow and indolent course
Presents with SOB, fever and dry cough
CXR may reveal diffuse granular opacities resembling ARDS, penumoatoceles or pneumothoraces
Definitive diagnosis is based on presence of organism in samples of induced suptum or from BAL or lung biopsy
How is PCP treated?
IV co-trimoxazole for 2-3 weeks +/- IV pentamidine
Second line is primaquine +clindamycin; atovaquone; trimethoprim +dapsone
Steroids given within 48-72 hours of diagnosis reduce the risk of respiratory failure, meachanical ventilation and death and are indicated if:
PaO2 < 9; A:a > 5
How is HIV treated?
Normally involves 3 antiretrovirals (ARV) - most commonly 2 NRTIs plus a protease inhibitor
describe necleoside reverse transcriptase inhibitors (NRTIs)
ARV drig
e.g. Lamivudine and zidovudine
Act as a false nucleotide and functions as a competitive inhibitor
s/es lactic acidosis, hepatic steatosis, rhabo
Describe non-nucleoside reverse transcriptase inhibitors (NNRTIs)
ARV drug
e.g. nevirapine
binds to reverse trascriptase and inhibits enzyme activity
s/es - hepatotoxicity
Describe protease inhibitors
ARV drug
e.g. saquinavir
Prevents processing of viral proteins
s/e/ SJS, dyslipidaemias
Describe fusion inhibitors
ARV drug
e.g. enfurviratide
Blocks fusion of HIV virus with host cell membranes
s/e/ GI side-effects
What are the challenges of HIV treatment on the ICU?
Continue pre-admission HAART
Input from ID/HIV pharmacist
1. Drug delivery - only zidovudine has an IV preparation. Others are tablets/capslues that can be crushed and used NG
2. Absorption may be affects by pathology. NG feed has to be interrupted to give certain ARVs. Gastric alkalinsation is CI’d with some ARVs
3. Dosing - changes in hepatic insufficiency and renal impairment
4. Interactions - benzos should be used with causiton with NNRTIs. NRTIs interact with numerous agents incl benzos, amiodarone, PPIs and H2RAs
5. Toxicity - can result in severe and life-threatening side-effects incl SJS, heoatic necrosis, pancreatitis and lactic acidosis
6. Immune reconstitution inflammatory syndorme (IRIS)
When should HAART be initiated in the HIV patient on ICU?
- AIDS-defining illness
- CD4 < 200cells/mm3
- Anticipated prolonged stay
- Deterioration despite optimal ICU management
Which patients can we test for HIV?
If knowledge of HIV status will make a difference to the treatment of a patient without capacity then it should be done
What is immune reconstitution syndrome?
There is a risk of precipitating IRIS on initiation HAART
Immune function begins to recover and then responds to the previously acquired opportunistic infection with an overwhelming inflammatory response
Treatment should be initiated against the offending organism. Supportive care is used and steroids are given in severe cases.
What are the AIDS - defining illnesses?
Candidiasis of the esophagus, bronchi, trachea, or lungs (but NOT the mouth) Cervical cancer Coccidioidomycosis Cryptococcosis, Cryptosporidiosis, Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision) Encephalopathy, HIV related Herpes simplex: chronic ulcer Histoplasmosis Kaposi sarcoma Lymphoma, Burkitt's (or equivalent term) Lymphoma Mycobacterium avium Mycobacterium tuberculosis Mycobacterium, other species Pneumocystis jiroveci pneumonia Pneumonia, recurrent Progressive multifocal leukoencephalopathy Salmonella septicemia Toxoplasmosis of brain Wasting syndrome due to HIV
What is the definition of ARDS?
2012 Berlin definition:
-ARDS is an acute diffused, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight and loss of aerated lung tissue with hypoxaemia and bilateral radiographic opacities, associated with increased venous admixture, increased physiological dead space and decreased lung compliance.
What is the oxygenation criteria for mild ARDS?
PaO2/FiO2 200-300mmHg (26.7-40kPa) + PEEP > 5
What is the mortality for mild ARDS?
27%
What is the oxygenation criteria for moderate ARDS?
PaO2/FiO2 ratio 100-200mmHg (13.3-26.7kPa) + PEEP > 5
What is the oxygenation criteria for severe ARDS?
PaO2/FiO2 ratio <100mmHg (< 13.3kPa)
What is the mortality of moderate ARDS?
32%
