Emergency Conditions Flashcards
What is anaphylaxis
A life threatening medical emergency caused by a severe type 1 hypersensitivity reaction
Immunoglobulin E (IgE) stimulates mast cells to rapidly release histamine and other pro-inflammatory chemicals, which is known as mast cell degranulation
This causes a rapid onset of symptoms, with airway, breathing and/or circulation compromise (which is the key diffentiation factor from a non-anaphylactic allergic reaction)
How does anaphylaxis present
History of exposure to an allergen
Rapid onset of allergic symptoms:
-Urticaria
-Itching
-Angiodema (swelling round lips and eyes)
-Abdominal pain
Additional symptoms:
-SOB
-Wheeze
-Swelling of the larynx, causing stridor
-Tachycardia
-Lightheadedness
-Collapse
How is anaphylaxis managed
Immediate medical attention and management
A to E:
-A - secure the airway
-B - provide o2, salbutamol and ipratropium bromide for wheezing
-C - provide IV bolus of fluids
-D - lie the patient flat to improve cerebral perfusion
-E - look for flushing, urticaria and angio-oedema, remove trigger
Once anaphylaxis diagnosed give:
-IM adrenaline, 1:1000 as per age related guidelines, repeated after 5 mins if required, if no improvement after 2 doses, give IM every 5 mins until adequate response, IV only given in secondary care
-Antihistamines, eg oral chlorphenamine or cetirizine
-Steroids, usually IV hydrocortisone
After:
-Observation - risk of biphasic reactions meaning a second anaphylactic reaction after successful treatment of the first
-Confirm by measuring the serum mast cell tryptase within 6 hours of the event
-Education and follow up with family trained in BLS and specialist referral and training in use of adrenalin auto injector
What are the indications for an adrenalin auto injector
Epipen, Jext and Emerade are trade names for adrenalin auto injector devices
Given to all children and adolescents with anaphylactic reactions and considered in those with generalised allergic reactions (without anaphylaxis) with risk factors:
-Asthma requiring steroids
-Poor access to medical treatment (eg rural)
-Adolescents, who are higher risk
-Nut ot insect sting allergies are higher risk
-Significant co-morbidities eg cardiac disease
How is an adrenalin autoinjector used
Confirm diagnosis of anaphylaxis
Prepare device by removing the safety cap on the non-needle end
Grip the device ina fist with needle pointing down
Administer injection by firmly jabbing the device into outer portion of the mid thigh until device clicks.
Can be done through clothing
Time to hold depends on brand (epipen 3 secs, jext 10 secs)
Remove the device and gently massage area for 10 secs
Phone emergency
Second dose may be given with new pen after 5 mins if required
What is sepsis
A condition where the body launches a large immune response to an infection that causes systemic inflammation and affects the functioning of the organs of the body
What is the pathophysiology of sepsis
Bacteria or other pathogens recognised by macrophages, lymphocytes and mast cells. These cells release vast amounts of cytokines like interleukins and tumor necrosis factor to alert the immune system of an invader. These cytokines activate other parts of the immune system
The immune activation leads to further release of chemical such as nitrous oxide that causes vasodilation. This immune response causes inflammation throughout the body
Cytokine cause endothelial lining of blood vessels to become more permeable, causing fluid to leak out of the blood and in to the extracellular space leading to oedema and a reduction in intravascular volume with the oedema around the vessels increasing space between the blood and tissues, reducing oxygen perfusion of tissues
Activation of the coagulation system leads to fibrin deposition throughout the circulation further compromising organ and tissue perfusion and leads to consumption of platelets and clotting factors as they are used up to form the clots within the circulator system. This leads to thrombocytopenia, haemorrhages and an inability to form clots and stop bleeding. This is known as disseminated intravascular coagulopathy (DIC)
Blood lactate rises due to hypoperfusion of tissues that starves the tissues of o2 causing the switch to anaerobic respiration, a waste product of that being lactate.
What is septic shick
When arterial blood pressure drops and results in organ hypoperfusion, leading to a rise in blood lactate as the organs begin anaerobic respiration.
Measured as either:
-systolic BP <90 despite fluid resuscitation
-Hyperlactaemia (lactate >4mmol/L)
How is septic shock treated
Aggressively with IV fluids to improve the BP and tissue perfusion
If IV fluid boluses don’t improve BP and lactate level then they need to escalate to HDU or ICU where they can use inotropes (eg noradrenalin) to stimulate the CV system and improve bp and tissue perfusion
What is severe sepsis
When sepsis is present and results in organ dysfunction:
-hypoxia
-oliguria
-AKI
-thrombocytopenia
-coagulation dysfunction
-hypotension
-hyperlactaemia (>2mmol/l)
What are the risk factors for sepsis
Any condition that impacts the immune system or makes the patient more frail or prone to infection is a risk factor:
-very young or old (<1 or >75 y/o)
-chronic conditions eg copd and diabetes
-chemo, immunosuppressants or steroids
-surgery or recent trauma or burns
-pregnancy or peripartum
-indwelling medical devices eg catheters or central lines
How does sepsis present
NEWS to catch signs
-temp
-HR
-RR
-O2 sats
-BP
-Consciousness level
O/E:
-signs of potential sources eg cellulitis, discharge from a wound, cough or dysuria
-non-blanching rash can indicate meningococcal septicaemia
-Reduced urine output
-Mottled skin
-Cyanosis
-Arrhythmias eg new AF
High RR (tachypnoea) often first sign of sepsis)
Elderly often present wtih confusion or drowsiness or simply “off legs”
Neutropenic or immunosuppressed patients may have normal obs and temp despite being life threateningly unwell
How is sepsis investigated
Arrange blood tests for patients with suspected sepsis:
-Full blood count to assess cell count including white cells and neutrophils
-U&Es to assess kidney function and for acute kidney injury
-LFTs to assess liver function and for possible source of infection
-CRP to assess inflammation
-Clotting to assess for disseminated intravascular coagulopathy (DIC)
-Blood cultures to assess for bacteraemia
-Blood gas to assess lactate, pH and glucose
Additional investigations can be helpful in locating the source of the infection:
-Urine dipstick and culture
-Chest xray
-CT scan if intra-abdominal infection or abscess is suspected
-Lumbar puncture for meningitis or encephalitis
How is sepsis managed
Hospital’s sepsis protocol
Assess and treat within 1 hour of presentation with suspected sepsis
Perform sepsis six (three tests and three treatments)
Escalate to senior and appropriate care level eg HDU or ICU if needed
Sepsis six:
-blood lactate
-blood cultures
-urine output
-O2 to maintain sats at 94-98% (or 88-92% in retainers)
-Empirical broad spectrum antibiotics
-IV fluids
What is neutropenic sepsis
Medical emergency
Sepsis in a patient with a low neutrophil count of less than 1 x10^9/L
Usually consequence of anti-cancer or immunosuppressant treatment
Treat any temp >38C in these patients as neut sepsis until proven otherwise
At high risk of death from sepsis as their immune system cannot fight the infection well enough
Need emergency admission and careful management
Treat with immediate broad spectrum antibiotics eg tazocin and other management is same as in sepsis but with extra precaution. Treat before results back, don’t wait!
What is shock
An abnormality of the circulatory system that results from reduced organ perfusion and tissue oxygenation
What are the causes of shock
Reduced cardiac output:
-Hypovolaemic shock
– Haemorrhage
— external
— internal
– Vomiting
– Diarrhoea
– Diuresis
– Burns
-Cardiogenic shock:
– MI
– Myocardial contusion
– Myocarditis
– Cardiac arrhythmia
– Negatively inotropic drug overdose (Beta blockers ir calcium channel blockers)
-Obstructive shock
– Tension pneumothorax
– Massive PE
– Cardiac tamponade
Reduced systemic vascular resistance (SVR):
-Septic shock
-Anaphylactic shock
-Neurogenic shock
How are BP, cardiac output, systemic vascular resistance, heart rate and stroke volume related
BP=COxSVR
CO=HRxSV
What is stroke volume
The volume of blood pumped by the heart per contraction
Determined by:
-preload
-myocardial contractility
-afterload
What is preload
The ventricular wall tension at the end of diastole and reflects the degree of myocardial muscle fibre stretch
Determined by volume status, venous capacitance and the difference between mean venous pressure and right arterial pressure
What is myocardial contractility
The intrinsic ability of the heart to work independently of preload and after load
What is afterload
Ventricular wall tension at the end of systole and is the resistance to anterograde blood flow
What is the pathophysiology of shock
Regardless of the cause of shock, inadequate organ perfusion tissue oxygenation results in cells switching from aerobic to anaerobic metabolism, generating a lactic acidosis that distrupts the cellular environment and causes myocardial depression
How is shock assessed
Assessment of severity:
-dyspnoea
-confusion
-light headedness
-drowsiness
-oliguria/anuria
-symptoms of the cause
O/E:
Airway:
-may be compromised due to reduced consciousness
Breathing:
-hypoxia secondary to::
– cause
– airway compromise
– apparent hypoxia due to pulse oximetry ineffective from peripheral shutdown
-tachypnoea
-Kassmaul’s breathing (hyperventilation to compensate for metabolic acidosis manifesting as “air hunger”)
Circulation:
-Cold, pale peripheries
-prolonged cap refill >2s
-Tachycardia
-Hypotension
-Oliguria
-Anuria
Disability:
-Confusion
-drowsiness
-unconsciousness
Signs of cause
Investigations:
-Bloods inclusing blood gas to check lactate
-ECG
-CXR
-Echo
-In trauma:
– Pelvic XR
– CT chest/abdo/pelvis as indicated
– FAST
How is haemorrhagic shock classified
Type I
-Volume of blood loss (ml): <750
-Percentage blood loss (%): <15
-Heart rate (beats/min): <100
-Blood pressure: normal
-Pulse pressure: normal/increased
-Respiratory rate (breaths/min): 14-20
-Urine output (ml/hour): >30
-Mental state: slightly anxious
Type II
-Volume of blood loss (ml): 750-1500
-Percentage blood loss (%): 15-30
-Heart rate (beats/min): 100-120
-Blood pressure: normal
-Pulse pressure: decreased
-Respiratory rate (breaths/min): 20-30
-Urine output (ml/hour): 20-30
-Mental state: mildly anxious
Type III
-Volume of blood loss (ml): 1500-2000
-Percentage blood loss (%): 30-40
-Heart rate (beats/min): 120-140
-Blood pressure: decreased
-Pulse pressure: decreased
-Respiratory rate (breaths/min): 30-40
-Urine output (ml/hour): 5-15
-Mental state: anxious, confused
Type IV
-Volume of blood loss (ml): >2000
-Percentage blood loss (%): >40
-Heart rate (beats/min): >140
-Blood pressure: decreased
-Pulse pressure: decreased
-Respiratory rate (breaths/min): >35
-Urine output (ml/hour): negligible
-Mental state: confused, lethargic
How is shock managed
Initial:
ABCDE assessment
Airway management
High flow 02 non-rebreathe to >94% sats
Obs monitoring
Three lead cardiac monitoring
ECG request
Portable CXR
Large bore IV access and take bloods and blood gas
Fluid resuscitation IV
Catheterisation and fluid balance monitoring (aiming output >0.5ml/kg/hr)
If BP fails to respond, refer to HDU/ICU for:
- central line insertion with central venous pressure and central venous oxygen saturation monitoring
- arterial line insertion and invasive arterial BP monitoring
- vasopressor and/or inotrope infusion
Further:
Identify and treat the cause:
-Haemorrhagic
– identify bleed and acheive control
– restoration of adequate circulating volume
— crossmatch blood and activate major haemorrhagic protocol
— transfuse o neg until cross matched blood available (ASAP)
– Correct coagulopathy by transfusion of platelets, fresh frozen plasma and cryoprecipitate as appropriate
-Septic
– antibiotics
– source control
-Anaphylactic
– adrenalin 0.5mg IM
-Tension pneumothorax
– needle thoracentesis
– intercostal chest drain insertion
-Cardiac tamponade
– Pericardiocentesis
– Thoracotomy
-Massive PE
– Thrombolysis
-Unstable tachyarrhythmias
– Synchronised direct current cardio version
-Unstable bradyarrhythmias
– Pacing
How will overdose/ poisoning present
Usually immediately after an accidental ingestion or inhalation of known drug or chemical but may present later in intential overdose
Acute confusional states
Hypoglycaemia
Abnormal liver function tests
Unexplained seizures
Abnormal bleeding
Several close contacts presenting with similar symptoms such as headache and confusion - ?CO poisoning in house
Recurrent or chronic unexplained symptoms in children (deliberate poisoning in Munchausen by proxy or factitious disorder)
What are the signs and symptoms of paracetamol overdose
Frequently asymptomatic
Symptoms:
Nausea and vomitting
Anorexia
Malaise
Abdominal pain
Altered mental status
Confusion
Evidence of previous self harm eg scars
Signs:
Asterixis
Bruising
Jaundice
Right upper quadrant pain
Oliguria/ anuria
Tachycardia/ hypotension
Coma
When is liver damage maximal in paracetamol overdose
3-4 days after overdose and may lead to liver failure, hypoglycaemia, encephalopathy, coma and death
How does aspirin overdose present
Hyperventilation
Tinnitus
Deafness
Vasodilation
Sweating
Coma in severe poisoning
How does tricyclic and related antidepressant overdose present
Dry mouth
Seizures
Coma
Cardiac conduction defects and Arrhythmias
Hypothermia
Hypotension
Hyperreflexia
Extensor plantar response
Convilsions
Respiratory failure
Dilated pupils
Urinary retention
How does SSRI overdose present
Nausea
Vomiting
Agitation
Tremor
Nystagmus
Drowsiness
Sinus tachycardia
Convulsions
Hyperthermia
Rhabdomyolysis
Renal failure
Coagulation deficiencies
Rarely can result in serotonin syndrome with marked neuropsychiatric effects, autonomic instability and neuromuscular hyperactivity
How does beta blocker overdose present
Bradycardia
Hypotension
Syncope
Conduction abnormalities
Heart failure
Drowsiness
Confusion
Convulsions
Hallucinations
Coma (in severe cases)
How do calcium channel blocker overdoses present
Nausea and vomiting
Agitation
Confusion
Dizziness
Coma
Metabolic acidosis and hyperglycaemia
Peripheral vasodilation and severe hypotension (in dihydropyridine calcium channel blockers)
Arrhythmias including heart block and asystole (Verapamil and diltiazem)
How does iron overdose present
Nausea
Vomiting
Diarrhoea
Abdominal pain
Haematemasis
Rectal bleeding
Hepatocellular necrosis and hypotension can occur later
Coma, shock and metabolic acidosis (in severe cases)
How does lithium toxicity present
Most offten in patients on long-term lithium and whose excretion of lithium is reduced due to dehydration or infection etc
Delayed onset of symptoms in deliberate overdose (12 hours or more)
Initially:
-apathy
-restlessness
Followed by:
-vomiting
-diarrhoea
-ataxia
-tremor
-weakness
-dysarthia
-muscle twitching
Severe poisoning:
-electrolyte imbalance
-dehydration
convulsions
-renal failure
-hypotension
-coma
How does opioid overdose present
Drowsiness
Coma
Respiratory depression
Pinpoint pupils
How is a paracetamol risk assessment carried out
Date of ingestion (any delay)
Timing of ingestion (single or staggered)
Time since last ingestion (staggered)
Weight (max calc use 110kg)
Pregnancy (use pre-pregnancy weight for toxicity and current weight for treatment)
Total amount ingested (mg/kg)
Current suicidal risk (consider MH assessment)
What are the significant doses in paracetamol overdose
<75mg/kg are unlikely to cause toxicity unless staggered
> 150mg/kg are associated with serious or fatal adverse effects from toxicity
Total doses >12g are potentially fatal
What is an acute ingestion of paracetamol
A potentially toxic dose of paracetamol taken within one hour or less
What is a staggered ingestion of paracetamol
Excessive ingestion of paracetamol over a period longer than one hour, usually in the context of self-harm
If time of ingestion is unknown then patients should be treated as a staggered overdose
What is the pathophysiology of paracetamol overdose
Paracetamol is primarily metabolised in the liver to non-toxic metabolites but in overdose these pathways become overwhelmed
Once ingested, paracetamol reaches peak conc at 4 hours within an average half life of 2 hours but this may be significantly increased in hepatic dysfunction patients
Metabolism occurs via conjugation with the addition of glucuronide to form a water soluble metabolite that can be excreted in urine. In overdose the conjugation become saturated and paracetamol is instead converted into the metabolite N-acetyl-p-benzoquinoneimine (NAPQI)
NAPQI has a short half-life and is usually conjugated by the addition of glutathione which is then renally excreted. If these stores are depleted then excess NAPQI binds to hepatocellular proteins and results in oxidative damage, mitochondrial dysfunction and hepatocellular injury.
What can effect glutathione reserves
(May increase the risk of severe hepatotoxicity)
Fasting
Excess alcohol consumption
Certain drugs
How is paracetamol overdose diagnosed and investigated
Diagnosis based on history
Investigations to assess for complications
Hospital admission:
-context of self harm
-symptomatic
-Ingestion of ≥75 mg/kg of paracetamol over an hour or less
-Ingestion of ≥75 mg/kg but the time of ingestion is uncertain
-Any patient who has taken a staggered overdose
-Ingestion of more than the licensed dose (4g/24 hours for adults) and the total dose is ≥75 mg/kg within 24 hours, OR, <75 mg/kg within 24 hours for each of the preceding 2+ days.
Bloods:
-FBC
-U and Es
-LFTs
-Bone profile
-Venous/ arterial blood gas
-Blood glucose
-Paracetamol levels
-Salicylates levels (always request in acute overdose)
What is a nomogram
Paracetamol ingestion graph used to determine if treatment with N-acetylcysteine (NAC) is needed
Plots paracetamol concentration against time from ingestio, if the paracetamol conc lies on or above the treatment line, NAC should be administered.
Used for patients who have ingested paracetamol over one hour or less and presented within 8 hours
As plasma paracetamol conc reaches its peak at 4 hours, it is important to take a paracetamol within 4 hours of the last ingestion
Start NAC in those with a delayed presentation; if paracetamol level will not be available within 8 hours from last ingestion; or staggered overdose
How is paracetamol overdose treated
Prinicple treatment is N-acetylecysteine (IV) (NAC)
NAC given as a standard 21 hour regimen which based on the patients weight
It comprises three consecutive infusions:
-First infusion (1 hour): 200ml 5% dextrose or 0.9% sodium chloride with 150 mg/kg of NAC
-Second infusion (4 hours): 500ml 5% dextrose or 0.9% sodium chloride with 50mg/kg of NAC
-Third infusion (16 hours): 1000ml 5% dextrose or 0.9% sodium chloride with 100mg/kg of NAC
After the 21 hour regimen, blood tests are taken to look for any signs of hepatic impairment. If evidence of significant coagulopathy, deranged liver function tests or abnormal renal function - discuss with liver transplant centre. Can then give the third infusion of NAC continuously back to back until further advice.
How does NAC work in paracetamol overdose
Multiple proposed mechanisms of action
Precursor to glutathione so administration increases the glutathione conc available to bind NAPQI
Risk of anaphylactoid in 30% of patients on regimen, usually occurs after first infusion with features of nausea, comiting, urticarial rash, angioedema, tachycardia and bronchospasm (shock is uncommon)
If adverse reaction happens, temporarily stop the infusion, consider chlorphenamine (antihistamine) and nebulised salbutamol. Once reaction has settled, restart the infusion - can consider slowing the rate of first bag to over 2 hours.
What is an anaphylactoid reaction
Same clinical picture to anaphylaxis but is not IgE-mediated
What is the treatment algorithm for paracetamol overdose
Acute ingestion (<8 hours ago)
-consider activated charcoal
-take paracetamol level at 4 hours
-blood tests
-nomogram
-if above treatment level, start NAC
Acute ingestion (8-24 hrs ago)
-paracetamol level
-bloods
-Start NAC if dose >150mg/kg
-Nomogram to help assess liver damage
-At risk then continue NAC
Acute ingestion (>24hrs ago)
-paracetamol level
-bloods
-Start NAC if jaundiced or hepatic tenderness
-Decision on NAC - continue if ALT raise or INR >1.3 or high paracetamol level
-At risk then continue NAC
Staggered overdose
-Treat with NAC
-Paracetamol level 4 hours after last ingestion
-Blood tests
-If at risk, continue NAC
When can NAC be stopped and when should it be continued
At the end of the standard 21-hour infusion of NAC, patients need to undergo repeat blood tests for LFTs, U&Es, INR and venous blood gas.
Treatment may be stopped when:
-INR ≤1.3 and ALT within normal range, OR
-INR ≤1.3 and ALT raised but <2x upper limit of normal and not more than double admission ALT
Treatment with NAC should be continued when:
-ALT >2x upper limit of normal
-ALT is raised and more than double the admission ALT
-ALT is raised and INR >1.3 (in absence of another cause)
-INR >0.5 from admission value
What is respiratory failure
Occurs when there is inadequate gaseous exchange in the lungs
it is defined by the partial pressure of O2 and CO2 in the arterial blood
Two types:
-Type 1 respiratory failure: is characterised by hypoxaemia (PaO2 < 8 kPa) and a normal or low CO2.
-Type 2 respiratory failure: is characterised by hypoxaemia (PaO2 < 8 kPa) and hypercapnia (PaCO2 > 6.5 kPa).
What is the aetiology of respiratory failure
Hypoxaemia is most commonly caused by a V/Q mismatch
Hypercapnia is often caused by alveolar hypoventilation
Number of process can lead to hypoxaemia and hypercapnia
What is V/Q mismatch
Ventilation to perfusion ratio
The ratio of alveolar ventilation to alveolar perfusion
In the average adult they are ventilated by 4L of air and perfused by. 5L of blood each minute, giving V/Q ratio of 0.8 (4:5)
There is normal for mismatch in V/Q to differ depending on the part of the lung eg better perfusion at the bases than the apices due to gravitational and hydrostatic forces; ventilation is also greater in the same way but to a lesser extent.
In disease, there may be an increase in the V/Q mismatch leading to hypoxaemia
Low V/Q refers to alveolar units with poor ventialation compared with perfusion resulting in hypoxaemia due to low alveolar o2 levels. May be seen in airway disease or interstitial lung disease where ventilation is reduced
High V/Q refers to alveolar units with poor perfusion compared with ventilation. This occurs in areas where perfusion is limited eg PE.
The hypoxaemia in V/Q mismatch normally responds well to O2 therapy by improving alveolar oxygenation in low V/Q areas
What is a shunt
Refers to blood entering the left side of the heart without first having travelled through pulmonary capillaries and participating in gaseous exchange
This can be thought of as an extreme version of V/Q mismatch (V/Q=0)
Shunts respond relatively poorly to oxygen therapy when compared to v/q mismatch as the shunted blood cannot be ventilated. Hypercapnia may occur if there is a high shunt fraction.
What can cause shunts
Pneumonia
ARDS
Pulmonary oedema
Alveolar collapse
What is diffusion limitation
The impairment of gaseous exchange across the alveolocapillary membrane
Can occur by:
-Reduced surface area of alveoli due to pathological destruction limiting the amount of lung tissue available for gaseous exchange
-Alveolcapillary membrane changes by inflammation and fibrosis, impairing diffusion across the membrane
Often seen in emphysema and lung fibrosis
Hypercapnia is less common than hypoxaemia as carbon dioxide is far more soluble and less likely to be affected
The hypoxaemia normally resonds well to O2 therapy
What is dead space in the lungs
Dead space represents areas of the lung that are ventilated but not perfused and therefore do not contribute to gaseous exchange
An extreme V/Q mismatch but the opposite of a shunt (V/Q=infinity, technically undefined)
Dead space can be:
-Anatomical - in the conducting airways where no gas exchange takes place
-Alveolar - caused by alveoli that are ventilated but not perfused
-Physiological - a combination of anatomical and alveolar
What causes an increase in alveolar dead space
Through destruction of pulmonary capillaries
Seen in:
-Emphysema (COPD)
-Interstitial lung disease
Results in a lower proportion of tidal volume engaging in gaseous exchange and leads to hypercapnia
What is type 1 respiratory failure
Characterised by hypoxaemia (PaO2 <8kPa) and a normal or low paCO2
Most commonly caused by V/q mismatch, but is also seen in shunts, diffusion limitationa dn alveolar hypoventilation
Can be acute or chronic
What are the signs of chronic type 1 respiratory failure
Polycythaemia (an increase in red cell mass in the blood)
Development of cor pulmonale
What are the common causes of type 1 respiratory failure
Pneumonia
COPD
Asthma
Pulmonary oedema
Pneumothorax
PE
Obesity
What is type 2 resp failure
Characterised by hypoxaemia (PaO2 <8kPa) and hypercapnia (PaCo2>6.5kPa)
AKA hypercapnic respiratory failure
Seen in conditions that result in alveolar hypoventilation
Can be acute or chronic depending on speed of onset and presence of compensatory mechanisms
What is acute T2RF
Can present with significant hypoxaemia, electrolyte disturbances, cardiovascular instability, loss of consciousness and ultimately cardiac arrest.
It is usually indicated by an acute insult (eg opiate overdose or acute exacerbation of COPD) with a new respiratory acidosis and no evidence of chronic compensation (eg normal bicarbonate)
What are the common causes of acute T2RF
Exacerbations of obstructive lung disease:
-COPD
-Severe asthma
-Cystic fibrosis
-Bronchiectasis
Respiratory depressants
-Opiate overdose
What is chronic t2rf
Evidenced by compensatory mechansisms seen on ABGs (or VBGs)
Increase in the Bicarbonate level occurs in the setting of chronic resp acidosis (can be in 30s when normal is 22-26)
Chronic resp acidosis may be fully compensated with a normal pH, elevated paCO2 and significantly elevated bicarbonate level
What are the causes of chronic respiratory acidosis
COPD
Asthma
Chronic neurological disorders (eg motor neuron disease)
Chronic neuromuscular disorders (eg myopathies)
Chest wall diseases
Obesity hypoventilation syndrome
What is oxygen induced hypercapnia
It is now understood that the development of oxygen-induced hypercapnia is multifactoral:
-Increased V/Q mismatch: increased O2 administration impairs hypoxic pulmonary vasoconstriction and results in increased V/Q mismatch and physiological dead space.
-Haldane effect: the presence of oxygen causes haemoglobin to have a reduced affinity for CO2. This results in CO2 being displaced from haemoglobin increasing the PaCO2.
-Decreased minute ventilation (less important than the above two factors)
COPD patients who are CO2 ‘retainers’ should generally have a lower saturation target of 88-92%.
What are salicylates
Group of medications of which aspirin is the most common
There are all NSAIDs and have a dual action as an antiplatelet at lower doses and an analgesic at higher doses
What is the pathophysiology of salicylate overdose
Mild toxicity:
-irritate gastric lining
-ototoxicity through multifactorial process involving reduced cochlear blood flow, secondary to vasoconstriction and changes to cochlear cells
Moderate/ severe toxicity:
-mixed respiratory alkalosis and metabolic acidosis
-stimulate the cerebral medulla, leading to hyperventilation and respiratory alkalosis
-metabolism of salicylates causes uncoupling of oxidative phosphorylation, resulting in anaerobic metabolism, causing heat production and pyrexia and increased lactic acid production, resulting in metabolic acidosis. The acidic effects of salicylates also contribute to the associated acidosis
-hyperventilation worsens in response to the acidosis until the body can no longer compensate
What are the typical symptoms of salicylate toxicity
Mild:
-Nausea and vomiting
-Epigastric pain
-Tinnitus
-Dizziness
-Lethargy
Moderate:
-Sweating
-Fever
-Dyspnoea
Severe:
-Confusion
-Convulsions
-Coma
What are the typical clinical findings in salicylate toxicity
Warm peripheries
Bounding pulse
Tachypnoea
Hyperventilation
Cardiac arrhythmia
Acute pulmonary oedema
How should suspected salicylate toxicity be investigated
Bed side obs
ECG - arrhythmias, QRS duration, QT prolongation
Cap glucose - to exclude hypo/hyper glycaemia
ABG- monitor acid base balance, initially hyperventilation will cause resp alk but then progress to met acidosis with partial resp compensation with normal or high pH
Plasma salicylate conc - >2 hours after ingestion and repeat every 2 hours till peaks
Plasma paracetamol conc in those with mixed overdose
FBC - exclude infection
U and Es - hyperkalaemia common, urea and creatinine may be raised, indicating AKI
LFTs - assess hepatic dysfunction
Coagulation - INR and prothrombin time may be increased in hepatic dysfunction
CT head - if altered mental state and intracranial pathology is suspected
How is salicylate toxicity diagnosed
TOXBASE classifies overdose as mild, moderate or severe based on clinical features and peak salicylate levels
Mild toxicity: <300 mg/L
Moderate toxicity: 300 to 700 mg/L
Severe toxicity: >700 mg/L
How is salicylate toxicity managed
A to E
No antidote so simply supportive care
ICU admission to be considered in moderate to severe toxicity
Initial management:
-Activated charcoal - if presenting within 1 hour of >125mg/kg ingestion
-IV fluid resuscitation - if volume depleted
-Potassium replacement - urgent hypokalaemia treatment with IV infusion to maintain plasma potassium at 4-4.5 mmol/L. Sodium bicarbonate therapy can precipitate hypokalaemia so any pre-existing hypokalaemia should be urgently corrected
-Sodium bicarbonate - reduces transfer of salicylates into the central nervous system and enhances urinary excretion of salicylates (aka urinary alkalinisation). Monitor urine pH (optimal 7.5-8.5).
Ongoing management:
-Cooling measures
-Haemodialysis - treatment of choic in severe salicylate poisoning with renal failure, severe metabolic acidosis or seizures
-IV Benzodiazepines - if frequent or prolonged convulsions
-CPAPA - if pulmonary oedema or acute lung injury, secondary to salicylate overdose
-Psychological support - if intential overdose
What is the difference between haemodialysis and haemofiltration
Haemodialysis involves the diffusion of solutes from a high concentration to a low concentration across a semipermeable membrane.
Haemofiltration uses convection and high pressure to force solutes from the blood to the dialysis fluid for disposal.
Haemodiafiltration combines the two processes.
WHat are the potential complications of salicylate poisoning
Acute respiratory distress syndrome (ARDS)
Seizures
Drug induced hepatitis
Cardiac arrest
WHat are the potential complications of salicylate poisoning
Acute respiratory distress syndrome (ARDS)
What are tricyclic antidepressents
A class of meds developed for severe depression but often now used for neuropathic pain and migraine prophylaxis
What are some examples of tricyclic antidepressants
Amitriptyline
Nortitiptyline
Dosulepin
What is reuptake inhibition
Prevents the neurotransmitter from being transported back into the pre synaptic neurone once released into the synaptic cleft and so the neurotransmitter sontinues to activate the postsynaptic receptor, increasing its effect
What is postsynaptic receptor antagonist
Prevents the neurotransmitter from activating the postsynaptic receptor overall reducing its effect
What is the mechanism of anction of TCAs
Reuptake inhibition (increased effect):
-Serotonin (5-HT receptors)
-Noradrenaline (NA receptors)
Postsynaptic receptor antagonism (decreased effect)
-Histamine (H1 receptors)
-A-1 adrenoreceptors
-Acetylcholine receptors
How does TCA overdose present clinically
Clinical manifestations of overdose become apparent within 6 hours of ingestion
Symptoms:
-dry mouth
-hot, dry skin
-confusion and hallucinations
-palpitations
Severe effects:
-arrhythmia
-cardiovascular collapse
-convulsions
-coma
A to E
A - risk of airway compromise
B - respiratory depression
C - myocardial sodium channel blockade resulting in hypotension and arrhythmias; serotenergic activity can causes tachycardia and peripheral vasodilation; ECG findings of widened QRS and prolonged QTc which predisopose to ventricular tachcardia and ventricular fibrillation
D - confusion, seizures and coma; check glucose too
E - hyperthermia due to serotenergic effects; anticholinergic signs including dry skin, eyes and mouth, urinary retention and ileus
What is serotonin syndrome
Potentially life threatening presentation
Overactivation of both central and peripheral serotonin receptors
Caused by serotonergic drugs (eg TCAs, SSRIs, some opioids)
Features:
-altered mental state
-neuromuscular hyperactivity
-autonomic hyperactivity
Clinical presentations:
-hyperntension
-tachycardia
-diaphoresis
-myoclonus
-hyperreflexia
-hyperthermia (severe cases)
-muscle rigidity (severe cases)
Clinical diagnosis with supportive management
How is TCA overdose investigated
Bedside:
-Obs (tachycardia, hypotension, hyperthermia)
-12 lead ECG (widened QRS and prolonged QTc, risk of VF and VT)
-Blood glucose (exclude hypoglycaemia)
-Blood gas (mixed acidosis - treat with bicarbonate)
Laboratory:
-FBC (base line)
-U and Es (hypokalaemia, renal impairment hx)
-Magnesium and bone profile (electrolyte disturbances can worsen arrhythmias)
-LFTs (in co-ingestion)
-Paracetamol and salicylate levels (checked in all with overdose especially in unclear history)
Imaging:
-No sepcific imaging but may be useful to do:
-CXR (in reduced consciousness level and airway compromise)
-CT head (should be considered in patients with significantly reduced GCS to rule out concurrent intracranial pathology. Also in those presenting with seizures)
How is TCA overdose managed
No specific antidote, so supportive management
Activated charcoal can be given to the conscious patient to prevent absorption if they present within one hour of ingestion
Sodium bicarbonate can be given in arrhythmia and acidosis to prevent progression to ventricular arrhythmias
A to E
A- airway manoeuvres or adjuncts or intubation is need definitive airway management
B- high flow O2 and start SpO2 monitoring
C- IV access, continuous cardiac monitoring in all unwell patients or those with an abnormal initial ECG, administer fluid bolus to hypotensive patients and sodium bicarbonate if cardiac arrhythmias occur
D- assess and monitor consciousness, Benzodiazepines should be given for seizures, phenytoin should be avoided due to its serotenergic effects
E- cooling measures for hyperpyredia, manage other symptoms as they develop (eg catheterise in urinary retention)
Mental health assessment required in intentional overdose
What are the potential complications of TCA overdose
If left untreated can result in death secondary to cardiac or neurological effects.
Prolonged seizure activity can result in brain injury and coma
Those with reduced consciousness are at risk of aspiration pneumonia if there airway is not managed effectively.
What is the mechanism of toxicity in iron overdose
Local GI effects followed by systemic effects (that do not occur without preceding GI toxicity following iron ingestion)
Local:
-corrosive injury to GI mucosa resulting in:
– vomiting
– diarrhoea
– haemetemesis
– melaena
– fluid loss which may result in hypovolaemia
Systemic:
-exact mechanisms are uncertain
-iron acts as a cellular toxin targeting the CV system and the liver, with secondary CNS effects, metabolic acidosis due to hyperlactaemia and free proton production from the hydration of free ferric ions, and coagulopathy
Overwhelms the normally regulated GI absorption of iron and bioavailability is greatly increased
Once absorbed, gradually mvoed intracellularly over 6 to 12 hours
Elimination is minimal
What is the risk assessment dose wise for iron overdose
<20mg/kg – asymptomatic
20-60mg/kg – GI symptoms only
60-120mg/kg – potential for systemic toxicity
>120mg/kg – potentially lethal
Note that this is based on the amount of elemental iron ingested. This varies considerably between different types of iron tablets, depending on the type of ferrous or ferric salt:
ferrous sulfate (dried) - divide dose by 3.3
ferrous sulfate (heptahydrate) - divide dose by 5
ferrous gluconate - divide dose by 9
ferous fumarate - divide dose by 3
ferric chloride - divide dose by 3.5
ferrous chloride - divide dose by 4
What are the clinical features of iron overdose
Follows 5 stages:
0-6 hours – vomiting, diarrhoea, haemetemesis, melena, abdominal pain. Significant fluid loseses may lead to hypovolemic shock
6-12 hours – gastrointestinal symptoms wane and the patient appears to be getting better. During this time iron shifts intracellularly from the circulation
12-48 hours – Cellular toxicity becomes manifest as vasodilative shock and third-spacing, high anion gap metabolic acidosis (HAGMA) and hepatorenal failure
2-5 days – acute heaptic failure, although rare mortality is high
2-6 weeks – chronic sequelae occur in survivors – cirrhosis and gastrointestinal scarring and strictures
What are the investigations for iron overdose
In addition to the usual screening tests in suspected tox cases (BSL, ECG, paracetamol level) the following specific tests can be useful:
serum iron concentration
-peak levels occur 4-6 hours following iron ingestion
-after 6 hours iron levels fall due to intracellular shift
-levels do not clearly correlate with clinical toxicity, but > 90 micromol/L (500 mcg/dL) is generally considered predictive of systemic toxicity (equivalent to >60mg/kg)
blood gas
-the presence of HAGMA is a useful marker of systemic toxicity
-in the absence of iron levels a serum bicarbonate level can be used as a surrogate marker
abdominal X-ray — can be used to confirm ingestion
LFTs, Coags — hepatic failure
UEC — renal failure
How is iron overdose managed
Resuscitation as indicated with concurrent specific assessment and management of the toxidrome.
Resuscitation:
-ABCs
-Priority is early restoration of circulating volume
-Resuscitate with boluses of 10-20 mL/kg crystalloid to prevent shock from gastrointestinal losses, vasodilation and third spacing
Supportive care and monitoring
-Ongoing assessment of response to resuscitation and antidotes
Decontamination:
-Iron not adsorbed by activated charcoal
-Whole bowel irrigation indicated for confirmed ingestions > 60 mg/kg (difficult and potentially hazardous in small children)
-Surgical or endoscopic removal of tablets if lethal ingestion (e.g. >120mg/kg) or WBI not feasible
Antidotes:
-Desferrioxamine chelation therapy in cases of systemic toxicity (high serum 1iron level or metabolic acidosis on ABG)
Disposition:
-Ingestion of >40/mg/kg in children should be assessed at hospital
-Those asymptomatic at 6 hours with a negative abdominal x-ray can be discharged home
-Those with symptoms are admitted to hospital and may require IV fluids (ward, HDU, ICU depending on severity; ideally a paediatric center)
-Patients with the potential for systemic toxicity may be best managed at larger hospitals where iron levels can be measured and iron chelation therapy administered if needed
-Consider neglect in children
-Psychiatric assessment in adults
DESFERRIOXAMINE
What is Desferrioxamine chelation therapy
An option for severe iron toxicity – the indications, duration and end-points of therapy are controversial.
Indications (may also be used in chronic iron overload)
-level >90 micromol/L at 4-6 hours post-ingestion
-evidence of systemic toxicity
-shock
-metabolic acidosis
-altered mental status
Mechanism of action
-chelates free ferric and ferrous ions in the plasma resulting in water soluble complexes that can be renally excreted
-removes iron bound to transferrin and hemosiderin in the vascular compartment (does not effectively remove iron from stores in other compartments)
-ferrioxamine is excreted unchanged in the urine, which classically turns a vin rose colour (although this is not a reliable indicator of chelation)
Administration
-initial IV infusion rate of 15 mg/kg/h, reduced if hypotension occurs, may be titrated up to 40mg/kg/h in severe toxicity
-cardiac monitoring is mandatory
-reconstitute the 500 mg powder with 5 mls sterile water and dilute to 100 mls with 5% glucose or normal saline
Adverse effects
-hypersensitivity
-hypotension (with rapid or high-dose IV administration)
-ARDS (with infusions >24h)
-toxic retinopathy
-Yersinia sepsis (the ferrioxamine complex is a siderophore that promotes growth)
Endpoints
-The infusion can be stopped when the patient is clinically stable and the serum iron level is <60 micromol/L
-usually about 56 hours therapy is sufficient
-treatment >24 hours is rare
