a staggering secret…

the case.

42 year-old-male presents to your Emergency Department via ambulance after being found unresponsive at home by his family. Paramedics found him to have a GCS of 5 and a blood glucose level of 1.9 mmol/L. This was treated with intravenous dextrose which subsequently improved his GCS to 13.

Past Medical History.

  • Schizoaffective disorder
  • Alcohol dependence

Medications.

  • Fluoxetine
  • Lithium

On examination.
Looks unwell. Visibly jaundiced ++.

A: Patent & protected.
B: Respiratory rate 24 per minute, SpO2 99% (room air). Chest clear to auscultation.
C: Warm peripheries. Pulse rate 107 per minute, Blood Pressure 95/60. Heart sounds dual without murmurs. No peripheral oedema.
D: GCS 11 (E4V1M6). Equal & reactive pupils (4mm). Moving all 4 limbs.
E: Temperature 36.8*C. Blood glucose (post-treatment) 4.6mmol/L.
F: Euvolemic.
G: Soft, non-distended abdomen with right upper quadrant tenderness. Active bowel sounds. No peripheral stigmata of chronic liver disease or coagulopathy.

At this time his family arrive to the department & report that he has not been his usual self for the past two weeks. He had been shutting himself away in his room with minimal oral intake. They report that he started to appear yellow around 2 days ago & today they found lots of empty medication packets in his bedroom…

  • Mild (compensated) metabolic acidosis:
    • HCO3 20, BE -4. pH 7.39.
    • Expected pCO2 = (1.5× 20) + 8 = 30 + 8 = 38.
    • Actual venous pCO2 of 34
    • ∴ likely a concomitant respiratory alkalosis.
  • High anion gap (Cl = 77)
    • = Na – (HCO3 + Cl)
    • = 130 – (20+77)
    • = 33.  
    • ∴ HAGMA secondary to severely elevated lactate
      However, need to check serum ketones, urea (9.8mmol/L) & an osmolar gap (serum osmol 297 mmol/L).
  • Severely elevated serum lactate (19mmol/L):
    • Type A (inadequate oxygen delivery)
      • Tissue hypoperfusion (shock, regional ischaemia)
      • Hypermetabolic state (sepsis/seizure)
      • Severe hypoxia or impaired oxygen utilisation (eg. CO/CN poisoning)
    • Type B (no evidence of inadequate oxygen delivery)
      • Underlying disease
      • Drugs & toxins
      • Inborn errors of metabolism
  • Other:
    • Moderately elevated serum creatinine
      • ?Acute vs Chronic renal failure
    • Mild hyponatraemia
    • Mild hypokalaemia
    • Normoglycaemic 

  • Paracetamol
  • Iron
  • Valproate
  • Metformin
  • Isoniazid
  • Linezolid
  • Alcohol (including propylene glycol)
  • Nucleoside reverse transcriptase inhibitors
  • Others:
    • Mushrooms (Amanita phalloides)
    • Anaesthetic gases
    • Carbon tetrachloride (Hydrocarbons)

Jaundice: Pre-hepatic (Unconjugated)

  • Overproduction of bilirubin
    (Extravascular/Intravascular haemolysis, Extravasation, Dyserythropoiesis, Cholelithiasis)
  • Impaired hepatic bilirubin uptake
    (Congestive cardiac failure, Porto-systemic shunts, Gilbert syndrome, Rifampicin, Probenacid)
  • Impaired bilirubin conjugation
    (Crigler-Najjar syndrome, Gilbert syndrome)

Jaundice: Hepatic (Conjugated)

  • Hepatocellular injury
    (Viral hepatitis, Alcoholic hepatitis, NASH, Drugs, Toxins)
  • Hypoperfusion
    (Sepsis, Cardiac failure)
  • Infiltration
    (Inherited diseases, Malignancy)

Jaundice: Post-hepatic (Conjugated)

  • Biliary obstruction
    (Cholelithiasis, Malignancy, Pancreatitis, Strictures, Primary sclerosing cholangitis, Cholangiocarcinoma)

Acute liver failure: (Most common causes)

  • Drugs
    (Paracetamol most common, Antibiotics, Statins, Antivirals, Antifungals, Antiepileptics, General anaesthetics, Iron, Recreational drugs, Herbal remedies, Carbon tetrachloride)
  • Viral hepatitis
    (Hepatitis C and B)
  • Alcoholic hepatitis
  • Toxin exposure (Amanita mushrooms) 

Acute liver failure: (Other causes)

  • Autoimmune hepatitis
  • Infiltration (Malignancy, Wilson disease)
  • Ischaemic hepatopathy
  • Budd-Chiari syndrome
  • Veno-occusive disease

  • Metabolic acidosis (described above)
  • Moderate-severe derangement of liver function
    • Predominate hepatitic picture (or hepatocellular injury) 
      • AST 1786, ALT 2751
      • AST/ALT ratio < 2:1 ∴ unlikely alcohol-induced liver injury
    • Associated severe jaundice/hyperbilirubinaemia (Bili 291)
    • Associated coagulopathy (INR 4.4)
    • Impression = highly concerning for fulminant liver failure
  • Normal PLT count, against the Dx of DIC or portal HTN with cirrhosis.
  • Elevated white cell count with neutrophilia & hyperlactataemia should trigger administration of empiric broad spectrum antibiotics.

No!

This scenario likely represents a staggered overdose. Also, the timing of this ingestion is unknown.

Fulminant liver failure secondary to Paracetamol toxicity

Resuscitation.

  • Support ABCs.
  • Intubation and mechanical ventilation:
    • Indicated if the patient is unable to protect their airway or maintain a patent airway in setting of cerebral oedema secondary to hepatic encephalopathy.
  • Obtain large bore peripheral intravenous access
  • Commence volume resuscitation with intravensous crystalloid and titrate to perfusion, pulse rate, mean arterial pressure >65mmHg, urine output and mental state
  • Commence vasopressors for fluid refractory shock

Treat precipitating factors.

  • Sepsis:
    • Empiric parenteral antibiotics
    • NB – Prophylactic antimicrobials with broad-spectrum coverage of gram-positive and gram-negative activity including an anti-fungal (e.g. piperacillin with tazobactam and fluconazole) should be administered on admission, as this halves the incidence of infective episodes when compared with commencement at the time of suspected infection.
  • Gastrointestinal haemorrhage:
    • Assess for haematemesis, melena or fall in haemoglobin.
    • Commence PPI ± octreotide infusion and urgent endoscopic treatment
  • Intentional toxin ingestion:
    • Commence available antidotes, specifically N-acetyl cysteine (see below)
    • Place under mental health act
    • Urgent mental health assessment
  • Acute kidney injury
  • Malnutrition

Treat complications.

  • Hypoglycemia:
    • Glucose 5-10% solution
    • NB. Concentrations >12% require administration via central venous line
  • Seizures: IV Midazolam 0.15mg/kg
  • Encephalopathy: PO/NG Lactulose 30ml every 2h (controversial in acute liver failure)
  • Cerebral oedema:
    • Common in grade III to IV encephalopathy
    • Liver transplantation is the only definitive treatment
  • Coagulopathy:
    • Intravenous Vitamin K 5-10mg
    • Consider FFP (15ml/kg) if actively bleeding
  • Electrolyte derangement:
  • Serial monitoring:
    • Glucose
    • Electrolytes
    • Coagulation studies
    • Liver and renal function
  • Paracetamol toxicity:
    • Commence N-acetylcysteine

Disposition.

  • Requires Intensive Care / HDU level care
  • Will need a Liver Specialist Unit if meeting transplant criteria

Massive paracetamol overdose can result in hepatotoxicity despite early treatment.

In the acute phase, administration of activated charcoal within 4 hours of overdose has been demonstrated to reduce paracetamol concentrations & lower rates of hepatotoxicity.

  • INR >3.0 at 48 hours or >4.5 at any time
  • Oliguria or creatinine > 200 micromol/L
  • Acidosis with pH < 7.3 after resuscitation
  • Systolic hypotension with BP < 80mmHg
  • Hypoglycaemia
  • Severe thrombocytopenia
  • Encephalopathy of any degree

Originally devised as prognostic criteria to predict patient survival without liver transplantation but now used as selection criteria for potential liver transplant recipients

Criteria include;

  • pH <7.3
  • INR >6
  • Creatinine >300
  • Presence of encephalopathy

Relative contraindications

  • Poor social support
  • Psychiatric illness likely to affect compliance

Patient was subsequently transferred to the intensive care unit of the regional liver transplant centre with decompensated liver failure secondary to paracetamol overdose.

The patient continued to receive the N-acetylcysteine infusion along with antimicrobial cover of tazocin and fluconazole.

Over the course of 10 days his LFTs & Coagulation profile returned to normal & his encephalopathy gradually resolved. He was subsequently transferred to a mental health facility for ongoing care.

References.

  1. Chiew et al (2016) ‘New Guidelines for the Management of Paracetamol Poisoning in Australia and New Zealand,’ Med J Aust 2015; 203 (5): 215-218
  2. Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology 2012; 55:965.
  3. Mas A, Rodés J. Fulminant hepatic failure. Lancet 1997; 349:1081.
  4. Stravitz RT, Kramer DJ. Management of acute liver failure. Nat Rev Gastroenterol Hepatol 2009; 6:542.
  5. Wai Kwan Lai, Nick Murphy; Management of acute liver failure, Continuing Education in Anaesthesia Critical Care & Pain, Volume 4, Issue 2, 1 April 2004, Pages 40–43, https://doi.org/10.1093/bjaceaccp/mkh013
  6. Chiew AL, Isbister GK, Kirby KA, Page CB, Chan BSH, Buckley NA. Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2) Clinical Toxicology. 2017; 55(10):1055-1065.

Author: Rosie Sayers & Daniel Gaetani
Web editing: Chris Partyka

concave considerations…

the case.

37 year old female presents to your Emergency Department complaining of shortness of breath and bilateral thigh pain after vomiting for one week.

It’s a busy day in the department, so whilst a bed is being organised the nursing staff have obtained IV access and taken the following venous blood gas…

  1. Moderate metabolic acidosis:
    • HCO3 16, BE -10.
    • Partially compensated with a pH 7.24
    • Exp pCO2 = (1.5x 16) + 8 = 24 + 8 = 32.
    • Actual = 39 (Likely due to VQ mismatch).
  2. High anion gap (Cl = 91)
    • 135 – (91+16) = 28
    • Delta ratio
      • = (28-12)/(24-16)
      • = 16/8
      • = 2 ∴pure HAGMA
  3. Severely elevated lactate: 9.8 mmol/L !!
    • DDx: sepsis, tissue ischaemia, medications…
  4. Moderately elevated serum creatinine
  5. Mild anaemia
  6. Mild hyperglycaemia
  7. Mildly low ionised calcium

The gas shows a high anion gap metabolic acidosis, specifically a lactic acidosis. This is likely driven by a Type 1 lactic acidosis due to tissue hypoxia and anaemia. Persistent vomiting is more likely to produce a metabolic alkalosis so this is not the driving force of this blood gas.

She is hypotensive at 90/60 mmHg and she is taken to the resuscitation bay where you meet her.

She rapidly states that she has heterozygous sickle cell disease.

Are all heterozygous patterns less severe?

No!
This lady was HbS/β0 thalassaemia compound heterozygous and of similar clinical severity to HbSS disease (see the table below for more detail).

Sickle cell disease genotypes. (Source: Wasil, 2011 – Ref#1)

She has had non-bilious vomiting for the past 5 days which she puts down to a viral gastroenteritis that she caught from her daughter. During this time she has likely fallen behind in hydration as she didn’t seek help until she “couldn’t bear the pain.” Today, she started to have breathing difficulties.

She describes a mild headache plus bilateral deep burning pain in her thighs. She is on hydroxyurea, denies pregnancy and states she has had all her vaccinations.

On examination:

  • A. Patent & protected.
  • B. Tachypnoeic to 32 breaths per minute. SpO2 93% on 15L via non-rebreather mask.
  • C. Tachycardic  (HR 121/min, sinus), Blood pressure 102/82 after an initial fluid bolus. Peripherally shut down and cool to touch. Dry mucosa.
  • D. GCS15, PEARL, no focal neurology.
  • E. Temperature 35.3*C. Appears lethargic++.
  • Other:
    • Abdomen soft with a mildly enlarged liver
    • No splenomegaly to suggest aplastic crisis.
    • No warmth in the leg joints to suggest sceptic joint or soft-tissue infection.

What conditions specific to sickle disease would account for her symptoms?

SICKLE CELL CRISIS

Acute chest syndrome.

The exact pathogenesis of acute chest syndrome (ACS) is unclear and is probably multifactorial. It is essentially an ARDS-subtype and clinically diagnosed with pulmonary alveolar consolidation.

Proposed mechanism for acute chest syndrome & vasoocclusive crisis in Sickle Cell Disease. (Source: Novelli, 2016 Ref#2)

  • Pulmonary infection:
    54% of patients admitted for ACS will have an infectious agent identified. Community acquired pathogens are most common. Despite increased risk of encapsulated bacteria due to functional hyposplenism these are isolated in only 10% of patients.
  • Fat emboli:
    80% are involved with vasoocclusive (VO) crisis and this lends itself to the theory that fat emboli with secondary ARDs may be the underlying pathology. Studies show 44% of patients that underwent a bronchoscopy during an ACS crisis had lipid-laden alveolar macrophages.
  • Haemolysis:
    Acute haemolysis coexists with a rise in LDH and dropping Hb. Mice models have shown that heme is necessary and sufficient to induce ACS.
  • Pulmonary infarction/PE:
    Given the prothrombotic state that sickle-cell patients are in during an acute crisis, they are susceptible to PE and lung parenchymal infarction. Literature suggests that PE is under diagnosed in this population despite the incidence actually being higher.

Vasoocclusive crisis (bony crisis).

“Sickling” causes microvascular entrapment of erythrocytes and leukocytes which lead to ischaemia. This leads to a subsequent inflammatory reaction that worsens the environment and encourages further sickling. The end product is necrosis that is felt as pain.

Mechanisms of vasoocclusion in Sickle Cell Disease
(Source: Montalembert, 2008 – Ref#3)

In this specific patient:

  • Sepsis:
    These patients are at risk of overwhelming sepsis. They have hypo/asplenism; so are vulnerable to encapsulated bacteria. She presented hypotensive & has an elevated lactate and should therefore receive empiric broad-spectrum antibiotics.
  • Cerebrovascular events:
    She had a mild headache but no focal neurological deficit. Ischaemic stroke was considered but the headache was thought to be due to skull bone vasoocclusive symptoms.
  • Multi organ failure:
    She had already developed an acute kidney injury and ARDS. During her admission she had deranged LFTs that normalised during her stay.
  • Septic arthritis:
    On inspection the legs were bone pain. Sickle cell patients (more common in paediatric patients) are at higher risk of sceptic arthritis.

  1. Oxygen:
    • Aim to maintain saturations >97%.
    • The peripheral pulse oximetry probe is unreliable and an ABG on room air should guide treatment (this also helps prognosticate for ACS/ARDS).
  2. Intravenous fluid:
    • Traditionally 1.5x maintenance fluid is required.
  3. Analgesia:
    • Pain crises are very painful and usually patients have tried opioids and escalating pain management regimens prior to attending hospital.
    • Morphine PCA (or equivalent) is usually required.
  4. Antibiotics:
    • Infection is a leading cause of ACS.
    • In this case we gave intravenous ceftriaxone.
  5. Investigations:
    • Biochemistry (Electrolytes, LFTs, CMP, βHCG)
    • Group & hold
    • Haemolytic screen, HbF
    • Infectious screen including Parvovirus B12, EBV/CMV & blood cultures
    • CXR
    • Arterial blood gas (preferably on room air)

Arterial blood gas (FiO2 0.60). A-a Gradient >170, metabolic acidosis, elevated lactate.

Anaemia with elevated Bilirubin & LDH consistent with haemolysis. Elevated WCC with neutropenia (?sepsis). Elevated creatinine (moderate AKI, ?pre-renal).

No.

There is usually a 24 to 72 hour delay in chest findings in a crisis. So a patient can have acute chest syndrome with a lag in radiological findings. It is a clinical diagnosis requiring the presence of hypoxia and dyspnoea to herald ACS.

In severe ACS/VO occlusive crisis after initial ED stabilisation the definitive treatments is plasma exchange. Essentially it aims to minimise the HbS load to <30% ( this number is institution dependent and some say <20%).

…..this patient had 8 units of PRBC and responded really well both clinically and biochemically. Her HbS went from 47% to 20%

This lady was Caucasian and presented with a sickle crisis most likely from dehydration secondary to her week of vomiting. She had a heterozygous phenotype that may have given some people false reassurance of her severity subtype. She got exchanged 8 units within 3 hours of presentation due to early involvement of Haematology and Intensive Care. This lady needed significant amounts of analgesia (at home prior to her presentation and in the Emergency Department). From a practical standpoint she had multiple antibodies in her blood and this made accessing suitable blood one of her rate limiting factors.

ACS carries a high risk of respiratory failure with 13% of patients requiring mechanical ventilation and a mortality rate of 9%. It is associated with prolonged hospitalisation and decreased overall prognosis. It remains the most common cause of death for this patient population. Ultimately, sickle cell disease is a terminal illness and these patients can get unwell quickly.

Fortunately this lady spent 48 hours in the ICU needing only the initial plasma exchange. She spent further time on the general ward in hospital and had a CTPA that showed a sub-segmental PE and was discharged with ongoing outpatient Haematology followup.

  1. Wasil, J (2011) Epidemiology of sickle cell disease in Saudi Arabia. Annals of Saudi Medicine 33(3):289-293.
  2. Novelli, E., Huynh, C., Gladwin, M.,Moore, C., Rangi, M(2012). Pulmonary Embolisation in Sickle Cell Disease: A case-control Study. Journal of Thrombosis Haemostasis. May 10(5):760-7663.
  3. Gladwin, M., Vinchinsky, E (2008) Pulmonary complications of Sickle Cell Disease. NEJM 2008: 359:2254-2265.
  4. EM: RAP: July 2017- Jonathan’s story. Dr Jessica Mason www.emrap.org.au
  5. Gladwin, M., Vichinsky, E (2008) Pulmonary complications of Sickle cell Disease. NJEM 359:2254-65
  6. Golman & Schafter. Goldman’s Cecil Medicine 24th edition. Ch166 Sickle cell disease and other haemoglobinopathies.
  7. Montalembert (2008) Management of sickle cell disease. BMJ v327
  8. Novelli, E., Gladwin, M (2016) Crises in sickle cell disease. Chest 149(4):1082-1093
  9. Yawn, B., Buchanan, G., Afenyi-Annan, A (2014). Management of Sickle Disease. Summary of the 2014 Evidence-Based Report by Expert Panel Members JAMA 2014; 312(10):1033-1048

 

Author: Courtney Peros
Web editing: Chris Partyka

canary in the mine…

the case.

16 year old female presents to your Emergency Department after falling from her mountain bike on a nearby track. As she fell to the ground, she reports landing on the handlebars which struck her upper abdomen.

She describes navigating a difficult section of a familiar track when her front wheel impacted a large tree root causing a loss of balance and the subsequent accident. A handlebar from her bike impacted her upper abdomen causing immediate pain and a moderate sized contusion. She has vomited once since the injury.

She otherwise appears to be ok.
– Was wearing a helmet at the time, did not lose consciousness and recalls all events.
– Has no dyspnoea, painful breathing or chest pain.
– Has no extremity pain, swelling or deformity.

She has no significant past medical history, takes no regular medications and has no known allergies.

On examination, she looks well but is in moderate pain.

  • A. patent & protected.
  • B. No chest wall crepitus, tenderness or emphysema. Respiratory rate 18/min. SaO2 98% (room air) Clear lung fields.
  • C. Warm and well perfused. Pulse rate 92 per minute. Blood pressure 110/68. No active external haemorrhage or long bone fractures.
  • D. GCS 15. Moving all 4 limbs. Pupils 5mm and reactive to light.
  • E. Well circumscribed abdominal wall contusion (~3 cm diameter) in the epigastrium, just left of the midline. She has moderate tenderness on deep palpation with voluntary guarding, but no rebound or percussion tenderness.

Your colleagues place a cannula and administer some analgesia.
During that time you grab your ultrasound …

The remainder of her images are normal.

Free fluid at the caudal liver edge & the splenorenal interface.

In the unstable patient with blunt abdominal trauma, the test characteristics of the FAST scan are impressive (Sn 73-88%, Sp 98-100%). However, in patients with penetrating trauma & in those with stable haemodynamics, this sensitivity falls away to 50% or less. This brings into question whether or not the FAST scan still has a role in the bedside assessment of these patients, where advanced imaging with contrast CT provides a greater level of diagnostic accuracy.

Here is a talk that I gave at the 2017 SWAN Trauma Conference on the role of the FAST scan in stable blunt trauma patients…

& here are the accompanying slides…

Despite her normal haemodynamics, this positive FAST scan signifies that she is carrying a significant intraabdominal injury & a high likelihood of clinical deterioration.

You notify your surgical colleagues & arrange an urgent abdominal CT…

  • Grade III splenic laceration (predominant grade II anterior laceration with other small subcapsular lacerations).
  • Intra parenchymal vascular injury is noted.
  • Small volume of free fluid.

Whilst your patient remains stable, with normal vital signs, the decision is made to proceed to interventional radiology. Here she undergoes selective angio-embolisation of a branch of the splenic artery.

She is admitted to the High Dependency Unit for overnight observation, where her haemodynamics and haemoglobin remain stable. Her recovery is uneventful and is discharged well 5 days later.

  1. Natarajan B, Gupta PK, Cemaj S, Sorensen M, Hatzoudis GI, Forse RA. FAST scan: is it worth doing in hemodynamically stable blunt trauma patients? Surgery. 2010; 148(4):695-700; discussion 700-1. [pubmed]
  2. Dammers D, El Moumni M, Hoogland I, Veeger N, ter Avest E. Should we perform a FAST exam in haemodynamically stable patients presenting after blunt abdominal injury: a retrospective cohort study Scand J Trauma Resusc Emerg Med. 2017; 25(1). [pubmed]
  3. Lee BC, Ormsby EL, McGahan JP, Melendres GM, Richards JR. The utility of sonography for the triage of blunt abdominal trauma patients to exploratory laparotomy. AJR. American journal of roentgenology. 2007; 188(2):415-21. [pubmed]
  4. Liu K. FAST Scan: Is it Worth Doing in Hemodynamically Stable Blunt Trauma Patients? The Journal of Emergency Medicine. 2011; 40(5):607-608. [link]
  5. Cho Y, Judson R, Gumm K, Cho Y, Santos R, Walsh M, et al. Blunt Abdominal Trauma. Trauma Service Guidelines: The Royal Melbourne Hospital; 2012. [link]
  6. Fleming S, Bird R, Ratnasingham K, Sarker S, Walsh M, Patel B. Accuracy of FAST scan in blunt abdominal trauma in a major London trauma centre International Journal of Surgery. 2012; 10(9):470-474. [link]
  7. Hsu JM, Joseph AP, Tarlinton LJ, Macken L, Blome S. The accuracy of focused assessment with sonography in trauma (FAST) in blunt trauma patients: Experience of an Australian major trauma service Injury. 2007; 38(1):71-75. [link]
  8. Bowra J, Forrest-Horder S, Caldwell E, Cox M, D’Amours SK. Validation of nurse-performed FAST ultrasound. Injury. 2010; 41(5):484-7. [pubmed]
  9. Behboodi F, Mohtasham-Amiri Z, Masjedi N, Shojaie R, Sadri P. Outcome of Blunt Abdominal Traumas with Stable Hemodynamic and Positive FAST Findings. Emergency (Tehran, Iran). 2016; 4(3):136-9. [pubmed]
  10. Matsushima K, Frankel HL. Beyond focused assessment with sonography for trauma: ultrasound creep in the trauma resuscitation area and beyond. Current opinion in critical care. 2011; 17(6):606-12. [pubmed]
  11. Richards JR, McGahan JP. Focused Assessment with Sonography in Trauma (FAST) in 2017: What Radiologists Can Learn Radiology. 2017; 283(1):30-48. [link]
  12. The Use of FAST Scan by Paramedics in Mass-casualty Incidents: A Simulation Study Prehosp. Disaster med.. 2014; 29(06):576-579. [link]