Article Notes
- A highly lipid-soluble alkylphenol.
- 2,6 di-isopropyl phenol
- 20 mL ampoules contain:
- 200 mg 1% propofol
- 10% soybean oil (solubiliser)
- 1.2% egg lecithin (emulsifier)
- 2.25% glycerol (make isotonic)
- Sodium hydroxide (buffer)
- pKa 11, pH 7
- 90% non-ionised @ pH 7.4
- weak acid
- stable at room temp, not light sensitive
- 1 mL = 0.1 g fat = 1.1 kcal
- Dose
- 2 mg/kg induction -> 2-6 mcg/mL
- 3-4 mg/kg in children
- 1 mg/kg load then: 10, 8, 6 mg/kg/h infusion (10m, 10m, cont) after 1 mg/kg loading - aims for blood conc of 3 ug/mL.
- Children: 15 mg/kg/h for 15 min, 13 mg/kg/h for 15 min, 11 mg/kg/h for 30 min then 9 mg/kg/h for 1-2 h, then 9 mg/kg/h for 2-4 h -> 3 ug/mL.
- Sedation 25-100 mcg/kg/min
- Plasma levels:
- major surg 4 mcg/mL (4-8 ug/mL)
- minor surg 3 mcg/mL
- 50% wake @ 1.07 mcg/mL (decrement lvl: 1.2 mcg/mL on TCI)
- 50% orientated @ 0.95 mcg/mL
- Psychomotor perfomance pre-op levels @ 0.3 mcg/mL
- Absorption - IV
- Distribution - Vdcc 0.5 L/kg, Vdss 2-10 L/kg
- Protein binding - 98% albumin
- Onset < 60s, peak 60-90s (slightly slower than thio: peak 30-60s); Offset 5-10 min (faster than thio).
- Metabolism - alpha1∆ 2 min, tß∆ 1h, CSHT-8h: 30 min. Conjugated to glucuronide & sulphate - water sol and renally excreted. 0.3% excreted unchanged.
- Clearance - 30 mL/kg/min.
- Children - larger central vol; longer CSHT (10m@1h & 20m@4h cf. 7m@1h & 10m@4h for adults); slower recovery; but require higher infusion rates and have higher clearance (req. same blood (=effect) conc as adults).
- NB: children have primarily pharmacokinetic differences not pharmacodynamic.
- Women - higher clearance.
- Mech - potentiates GABA inhibition.
- CNS - anaesthetic, anticonvulsant (?), antiemetic, antipruritic, amnesic.
- Not ant-analgesic like thio.
- Inc interthreshold range for temp
- CVS - 25-45% dec MAP, dec CO, dec SVR (dec SNS outflow; direct effect on veins, dec intracellular Ca mobilisation), HR unchanged (resets barorec response).
- Resp - resp depression (apnoea in 30% alone, 100% + narcotic), dec TV, inc RR, bronchodilation (slight), dep laryngeal reflexes.
- Renal - dec RBF, green urine.
- GIT - antiemetic, no hepatic effects.
- Haem - intralipid dec platelet aggregation.
- SEs - anaphylaxis rare; sig hypotension in volume depleted; hallucinations; abuse.
- pKa - 7.3 (58% nonionised @ 7.4)
- Octanol water coeff - 18
- phenylpiperidine opioid
- contain 2 ester bonds so hydrolysed by non-specific tissue esterases.
- Preparation contains 'glycine', so cannot be used epidurally.
- White powder for reconstitution with water - 1, 2, 5 mg packs
- Dose: (100x morphine potency, ~equal to fent)
- TCI: 3-8 ng/mL
- (up to 15 ng/mL for very stimulating procedures)
- Spontaneous ventilation returns @ 1-2 ng/mL
- 0.1-0.3 mcg/kg/min infusion (with propofol 80 mcg/kg/min (= 34 mL/h for 70 kg).
- 0.01-0.05 mcg/kg/min spont vent
- dilute 1 mg to 50 mL = 20 mcg/mL, or 5 mg in 50 mL = 100 mcg/mL.
- paeds: 0.03 mg/kg in 50 mL then 1 mL/h = 0.01 mcg/kg/min.
- Or paediatric whole-ampoule dilutions when advanced pumps are unavailable:
- 1mg in 16.7mLs
- or 2mg in 33.3 mLs
- or 3mg in 50mLs
- → to give a dilution of 60mcg/mL
- then for a patient of XYkg running at X.Y mLs/hr is 0.1mcg/kg/min. eg. for a 42kg patient running at 0.1mcg/kg/min will be 4.2mLs/hr which over 4 hrs uses 16 mL so a 1mg ampoule would be sufficient.
- 1 mcg/kg IV bolus to blunt pressor resp to intubation, better than fentanyl. (equiv. fent 2 mcg/kg, alfent 20 mcg/kg)
- 3-5 mcg/kg for intubation with propofol 2 mg/kg.
- 0.2-0.8 mcg/kg bolus for PCA analgesia (++SEs: sedation, desaturation)
- Absorption - IV
- Distribution - 0.5 L/kg (small)
- Protein binding - 70-90%
- Onset 1-4 min; Offset 4 min (offset due to metab not redist)
- Metabolism - ß½ ~10 min. (CSHT-8h only 4 min!) Metabolised by non-specific plasma esterases to almost-inactive metabolites (GR90291: 1/4600 activity! / t½ 2h).
- Minor pathway - N-dealkylation. NOT metabolised by plasma cholinesterase.
- Clearance - 42 mL/min/kg (30-50% CO)
- Mech - highly selective mu agonist.
- CVS - dec MAP & HR 20-30%. (? low dose glycopyrrolate to attenuate brady).
- No histamine release.
- CNS
- max MAC reduction ~ 85% (0.1-0.2 mcg/kg/min = 60-70% MAC reduction).
- To avoid awareness keep propofol @ at least 80 mcg/kg/min or volatile 0.3 MAC.
- Sedation.
- Beware rapid Opioid Induced Hyperalgesia.
- Resp - ⇣ RR & MV; apnoea. Spontaneous respiration occurs at blood concentrations of 4 to 5 nanogram/mL in the absence of other anaesthetic agents; for example, after discontinuation of a 0.25 microgram/kg/minute infusion of remifentanil, these blood concentrations would be reached in two to four minutes.
- GIT - dec CTZ stimulation as rapidly metabolised; no ion trapping.
- Muscle - muscle rigidity similar to alfentanil, though more than fentanyl.
- May cause chest wall rigidity (inability to ventilate) after single doses of > 1 microgram/kg administered over 30 to 60 seconds or infusion rates > 0.1 microgram/kg/minute.
- Administration of doses < 1 microgram/kg may cause chest wall rigidity when given concurrently with a continuous infusion of remifentanil.
- Foetal - little effect as rapidly metabolised by foetus.
- Semi-synthetic thebaine derivative (like oxycodone).
- Partial µ-agonist.
- Dose: 0.5 mg q6h IV/IM
- 30x morphine potency
- 200mcg-400mcg sublingual qid for analgesia
- Absorption - IV, IM, s/l, epidural (po undesirable as ++ 1st pass met)
- Distribution - 3 L/kg
- Protein binding - 96%
- Onset 30 min; Offset 4 h (longer latency & duration than morph)
- Metabolism - ß½ 5 h; hepatic dealkylation & glucuronidation. Excreted in bile & hydrolysed by GIT bacteria.
- Clearance - 14 mL/min/kg (dec 30% by GA)
- Mechanism: µ partial agonist.
- 50x greater mu rec affinity than morphine.
- May be used to treat heroin/morphine dependence.
- Greater lipid solubility than morphine.
- Ceiling effect to both analgesia & respiratory depression.
- Long duration as slow to dissociate from receptor & thus difficult to reverse.
- "Dissociative anaesthesia" refers to dissociation of thalamocortical and limbic systems on the EEG.
- phenylcyclidine (PCP) derivative
- pKa 7.5, weak acid (like thiopentone 60% nonionised @ pH 7.4)
- highly lipid soluble (4x thio)
- ampoule: 200 mg in 2 mL
- acidic solution of i) ketamine hydrochloride with ii) benzethonium chloride (preservative - neurotoxic !)
- 2 optical isomers - S(+)d ketamine has i) more rapid emergence due to higher metab, ii) less emergence SEs, iii) less cardiac depression, iv) 3x analgesic potency.
- Dose - 1.5-2 mg/kg IV, 10 mg/kg IM
- oral premed: 6-7 mg/kg po (15-30 min onset)
- Rx: asthma 20 mcg/kg/min
- analgesia: 0.1-0.3 mg/kg/h (no dysphoria @ 0.1, sometimes pleasant dreams @ 0.2 mg/kg/h). -[HPH 400mg in 50mL]
- TIVA: 10-50 mcg/kg/min
- Absorption - IV, IM, oral or PR
- Distribution - 8 L/kg
- Protein binding - 25% (thiopentone 75%, propofol 98%)
- Onset IV: 45-60s, peak 60s; IM: 3-5 min; Offset 15-30 min
- Metabolism - alpha∆ 11 min, ß ∆ 2.5 h. Hepatic p450 to N-demethylation to norketamine, hydroxylated to hydroxynorketamine, conjugated to water sol glucuronide derivatives.
- Norketamine has 1/5 activity of ketamine (? post-op S/Es).
- Clearance - 18 mL/kg/min (prop 25, thio 4 mL/kg/min)
- Mech - non-competitive NMDA antagonism (PCP site on NR1 subunit); anti-muscarinic; anti-monaminergic; inhibits peripheral reuptake of catecholamines; S+ enantiomer has some mu receptor activity; inhibits NO synthesis; inh non-NMDA glutamate rec.
- CNS - analgesia, amnesia, dissociative anaesthetic (thalamocortical - limbic system); inc CBF, CMRO2, ICP & IOP.
- CVS - direct cardiac depressant, but inc SNS outflow - inc CO, HR, MAP. Variable Vc & Vd.
- Resp - unaltered response to CO2; bronchodilator; inc salivary secretions; airway reflexes intact.
- GIT- inc BSL
- SEs - PONV, emergence delerium, ++ secretions, uterine hypertonicity at > 1.5 mg/kg
- Interactions - halothane prolongs duration by delaying its redistribution and metabolism.
- Characteristically : eye open, slow nystagmus, varying purposeful movement and hypertonus unrelated to stimuli
- Advantages: sympathetic stimulation with preservation of BP esp in hypovolaemic state, preservation of airway reflexes, bronchodilation and intense analgesia
- Disadvantages: can theoretically precipitate myocardial ischaemia (increasing both workload and O2 requirements) increases CBF, increases PVR, emergence delirium (also anaesthetic end-point unclear and uncontrolled movements).
- Support ICU needs of those with COVID.
- Make hospitals safe for patients both with and without COVID.
- Returning staff and services to pre-pandemic areas as possible.
- Protect staff with adequate personal protective equipment.
- Appropriate surgical case triage.
A. Physiochemistry
B. Pharmacokinetics
C. Pharmacodynamics
A. Physiochemistry
B. Pharmacokinetics
C. Pharmacodynamics
A. Physiochemistry
B. Pharmacokinetics
C. Pharmacodynamics
Ketamine is a dissociative anaesthetic & potent analgesic.
A. Physiochemistry
B. Pharmacokinetics
C. Pharmacodynamics
Ketamine produces a dissociative state (unconsciousness where in cataleptic state, disconnected from surroundings associated with functional and electrophysiological dissociation between thalamo-neocortical and limbic system)
Although Taiwan has geographic, commercial and social proximity to China, it stands as a stark example of success in response to the SARS-CoV-II pandemic.
"Despite being close to China, Taiwan has stopped the COVID-19 with general screening strategy and encouraging people in Taiwan to wear a mask. Taiwan reported the first COVID-19 case on January 21, 2020. About 850,000 and 400,000 of Taiwan's 23 million citizens live and work in mainland China, respectively."
Many factors have contributed to this success, beginning with Taiwan's memory and lessons drawn from the 2003 SARS-I pandemic.
Two notable factors are Taiwan's national health service, with it's ubiquitous and affordable access to acute medical care:
"Taiwanese people … can go to the emergency department of the nearest hospital for relevant medical examinations (including sampling and testing for COVID-19, blood tests, and X-ray imaging test) with out-of-pocket medical expenses of less than NT$ 600 (USD 20). People with high suspicion of COVID-19 infection will be admitted to isolation wards, and those who have tested positive for COVID-19 can only be discharged home after three consecutive respiratory specimens test negative for the virus. … patients will have to pay less than NT$ 3000 (USD 100) out-of-pocket for medical services."
And their management of mask access, production and subsequent widespread public use:
"The daily production capacity of face mask manufacturers in Taiwan before the outbreak was 1.88 million face masks ... Currently, Taiwan is capable of producing 20 million face masks per day and will boost its production capacity to 25 million face masks per day."
Why is this important?
Indications for the use of laryngeal mask airways (LMAs) increasingly challenge our airway choice for surgical procedures where endotracheal intubation has been the norm. Thyroid surgery, with its limited anaesthetic access to the airway and potential for airway obstruction, has not typically been a first choice for LMA use.
Proponents point to avoiding muscle relaxants and reducing throat pain and laryngeal trauma as the main benefits.
What did they do?
Gong and team randomised 138 ASA 1 & 2 adults to either flexible (reinforced) LMA or intubation with an ETT (7.0 or 7.5 mm). Notably any patients with surgical complexity or BMI > 30 kg/m2 were excluded. The study was single-blinded.
Concluding
The researchers reported the upper 95%-CI for estimated mean difference in peak airway pressure as +0.96 cmH2O, and for endtidal-CO2 +1.99 mmHg – neither of which are clinically significant.
They concluded that flexible-LMA was non-inferior to ETT in terms of PAP and ET-CO2.
Hang on...
The relevance of this study to most thyroid surgical patients is however limited at best. Not only were common groups of patients excluded (ie. BMI > 30) but one of the major arguments for LMA use (avoiding muscle relaxants) was irrelevant: all patients were paralysed with rocuronium.
Further, in 7% of the LMA cases severe air-leak occured and the surgical team were asked to cease or reduce tracheal traction.
Be smart
Although the journal editors conclude in their Key Points that "FLMA is a safe alternative for experienced anesthesiologists in thyroid surgery" this seems quite a stretch given that this small study was neither powered for safety and only investigated airway ventilation performance as a narrow surrogate for acceptability.
Additionally the authors themselves highlight very real surgical concerns that LMA use can distort pharyngeal anatomy with serious consequences.
Not dissimilar to arguments for LMA use in GA caesarean section, the use of an LMA for thyroid surgery edges toward 'just because we can, does not mean we should'.
Fascinating introspection from an experienced psychiatrist on the ways the pandemic has subtly (and perhaps not-so-subtly) changed his interactions with patients and his perspective on his role as caregiver.
"...among the many unknown — and potentially positive — outcomes of the pandemic, one may be the more widespread realization that “acting like a doctor” ideally involves less acting and more authenticity."
Why is this interesting?
Digital radiology systems (PACS) allow point-of-care enhancement and adjustment of x-ray images. 'Inverted grayscale' viewing has been advocated as a way to improve the ability to detect small pneumothoraces on posterior-anterior chest x-rays (CXR).
This case-control cross-over study challenges this practice.
What did they do?
The researchers used CXRs of 106 adult patients with a known spontaneous pneumothorax and 162 matched-controls without pneumothorax, but who had presented with pneumothorax-consistent symptoms.
Using a senior radiologist as the gold standard diagnostician, two groups of five emergency physicians were then allocated to identify the presence of a pneumothorax in all 268 CXRs – one group using inverted grayscale and the other the conventional digital view.
To ensure the groups were comparable, the researchers also had each review a random selection of both inverted and conventional images, and compared how the group diagnostic sensitivities correlated.
Bottom-line:
Surprisingly, the sensitivity of pneumothorax detection was higher for conventional imaging than when using inverted grayscale (91.7% vs 84.5%). Specificity was comparable.
Be smart…
Although the researchers showed the inferiority of isolated inverted-grayscale imaging compared to conventional, it is a technique almost always used alongside first viewing a CXR with conventional contrast. Thus even if inferior, it is unlikely to undermine the diagnostic sensitivity of standard CXR reporting.
Figure 2 from the study shows overall recovery and for each domain between neostigmine (N) and sugammadex (S) at each time point (15 min, 40 min and Post-Op Day 1).
A significant difference was observed in physiological recovery at 15 min after surgery, but not for overall recovery or any other domain.
Cook and Harrop-Griffiths survey the damage of a health system stretched to its limits in response to the UK's COVID-19 crisis, and how elective surgery could be carefully recommenced – particularly considering that the pandemic is far from over.
"....this has been achieved ‘by the skin of our teeth’ and until very recently, the threat of insufficient ICU beds, ventilators, and the need for triage were all anticipated: a few hospitals were overcome by the surge of critically ill patents."
They highlight several priorities as the NHS looks to return to a 'new normal' of healthcare provision:
"Having weathered the COVID‐19 storm, we are now being asked to assess the damage done, pick up the pieces and rebuild. However, this storm will rage for many months. Flattening the epidemic curve does not reduce the total number of cases but spread their burden over a longer period of time..."
Of particularly note is the challenge of ensuring COVID positive patients do not undergo non-essential surgery, known to be associated with a high post-operative mortality. They explore the complexities of pre-operative isolation and testing (PCR or CT), and the inherent limitations of these.
"The move from a health service focused on one single disease to one that continues that challenge while also addressing all the other health needs of the population may be even harder than that the crisis phase that preceded it."