British journal of anaesthesia
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Review
Propofol infusion syndrome: a structured literature review and analysis of published case reports.
Propofol infusion syndrome is a rare, potentially fatal condition first described in children in the 1990s and later reported in adults. We provide a narrative review of what is currently known about propofol infusion syndrome, including a structured analysis of all published case reports; child and adult cases were analysed separately as propofol is no longer used for long-term sedation in children. The review contains an update on current knowledge of the pathophysiology of this condition along with recommendations for its diagnosis, prevention, and management. ⋯ The cumulative dose of propofol was associated with an increased number of clinical features and the number of organ systems involved in adult cases only. Clinicians should consider propofol infusion syndrome in cases of unexplained metabolic acidosis, ECG changes, and rhabdomyolysis. We recommend early consideration of continuous haemofiltration in the management of propofol infusion syndrome.
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This thorough review of the global epidemiology of perioperative hypersensitivity (POH), reflects our increasing awareness that anaphylaxis varies geographically.
Incidence
Reported incidence ranges from 1 in 18,600 to 1 in 353, although NAP6 (UK) and French studies independently estimate life-threatening anaphylaxis at 1 in 10,000.
Mortality
Anaphylaxis mortality was generally ~4% (UK, France, USA, Japan), although Western Australian data estimated a lower range of 0-1.4%.
Causal agents
Implicated agents commonly include neuromuscular blocking drugs (1st or 2nd commonest in most studies), although the higher incidence seen with specific NMBDs (eg. Sux and Roc) appears to occur in some regions but not others. Pholcodine has been implicated as causative in these regional differences.
Sugammadex has increasingly been implicated as a cause of POH, though notably also with regional variation. A dose-related effect has also been reported.
Antibiotics are an increasingly common cause of POH, in particular β-lactams. Nevertheless, ‘pan-β-lactam allergy’ is probably rare, and some examples like cefazolin, have limited cross-reactivity.
“Cefazolin does not share an R1 and R2 group with any other β-lactam...”
Latex POH is declining, while chlorhexidine is increasing (9% in NAP6, with significant regional variability), albeit often as a ‘hidden’ precipitant.
Surgical dyes (patent blue V, isosulfan blue, methylene blue) are also increasingly common causes of POH (4th most common in NAP6 (~1 in 7,000), 3rd in France).
Less common POH causes include povodine-iodine and colloids.
Hypnotics, local anaesthetic, aprotinin, protamine and NSAIDs are very uncommon-to-rare causes of POH. Opioids are sometimes implicated via the MRGPRX2 receptor, although true opioid IgE-mediated hypersensitivity is very rare.
Bottom-line
The wide geographic variations in anaphylaxis incidence and causation reveal a complex interplay of genetics and environment, along with our evolving understanding of the complexity of anaphylaxis.
Go deeper...
Read Florvaag & Johansson’s seminal article The Pholcodine Story for an intriguing story of geographic POH differences.
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Review Meta Analysis
Low-dose ketamine in painful orthopaedic surgery: a systematic review and meta-analysis.
Low dose ketamine reduces pain and opioid requirements in the first 24 hours after major joint surgery.
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Children who are exposed to multiple general anaesthetics before age three demonstrate deficits on neurosphycological testing, although not children with a single exposure.
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Review
Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review.
The systemic antinociceptive effects of lidocaine occur by mechanisms other than sodium channel blockade, including silencing of ectopic discharges, inflammatory suppression, and neurotransmission modulation.
pearl