General Flashcards
Oxyhaemoglobin dissociation curve (RCoA old book)
Oxygen delivery (Mendonca)
Fetal Hb has a lower P50 (left shift) so loads with O2 more readily. It has a higher SpO2 at a given PO2 than adult Hb. Fetal Hb is 2 alpha and 2 gamma subunits. It is the beta subunits that bind to 2,3DPG and cause the curve to move rightward, hence the fetal curve remains leftward.
Lactic acidosis type A: caused by tissue hypoxia; low CO, severe anaemia, regional hypoperfusion
Type B: absence of hypoxia e.g. DM, renal failure, hepatic failure, biguanides, salicylates, isoniazid, haem malignancies, AIDS, inborn errors of metabolism
Hyperbaric O2: CO poisoning (e.g. preg/MI), severe anaemia, anaerobic sepsis/gas gangrene, decompression sickness, gas embolism, compromised skin grafts/flaps, osteomyelitis. Increases dissolved O2 in arterial blood, reduces gas bubble size, causes vasoconstriction, increases BP and SVR, promotes new vessel formation and wound healing, prevents growth of anaerobic bacteria and production of clostridial toxins, reduces oxygen free radicals thereby reducing reperfusion injury.
SEs of hyperbaric O2
High pressure: tympanic perforation, decompression sickness.
High FiO2: pulmonary, neurological and systemic toxicity. Pulmonary (Lorrain Smith) = absorption atelectasis, oedema, alveolar haemorrhage, inflammation, fibrin deposition and alveolar thickening. Neuro (Paul Bert - Bert for brain) = muscle twitching, nausea, tinnitus, vertigo, hallucinations, dysphoria, visual field defects; seizures occur at 2-3atm. Systemic = due to arterial PO2 rather than alveolar. Retrolental fibroplasia in premature neonates occur with PaO2 10-20kPa for a few hours. Reversible myopia. Hypoxic drive in 10% COPD pts.
FiO2 1.0 for 12-24h causes irritation and sternal discomfort.
FiO2 1.0 for 24-36h causes reduced vital capacity, reduced compliance and diffusing capacity, reduced surfactant production, V/Q mismatch and increased capillary permeability.
Bleomycin causes pulmonary toxicity which is exacerbated by O2. Aim SpO2 88-92%.
BTS guidance O2 prescribing - rx on admission and specify target SpO2.
CO poisoning: CO has 200x affinity than O2 for Hb. Left shift. Reduces Hb available for O2 transport.
CNS - headache, dizziness, seizures, LOC. CVS - tachycardia, MI, arrhythmias. RS - tachypnoea, pulmonary oedema. Metabolic acidosis. False high SpO2 reading.
100% reduces half life from 5h to 1h. Hyperbaric O2 reduces it to 20m, and also provides alternative oxygenation via dissolved O2. Also dissociates CO from cytochrome oxidase.
Hypothermia and blood gases (RCoA old book)
pH rises by 0.0147 units/degree C fall in blood temp (Rosenthal factor) as pCO2 falls
Favours heart and brain flow during hypothermia on CPB
Can add CO2 to oxygenator
Hibernating animals hypoventilate for this reason
Alpha stat and pH stat
Consequences of hypothermia
CVS - increased myocardial O2 demand, ischaemia, arrhythmias/brady/J etc, vasoconstriction, high SVR
RS: increased VO2 with shivering, increased PVR, V/Q mismatch, impaired HPV, reduced ventilatory drive, increased dead space, increased gas solubility
Haem: coagulopathy (enzymes temp dependent), reduced plt function, L shift of curve
Metabolic: BMR reduces 5-7% per degree C if not shivering, metabolic acidosis, hyperglycaemia (reduced insulin), K+ rise on rewarming
Renal: low RBF/GFR
GI: low blood flow, reduced gut motility
mild: 32-35 C
moderate: 28-32 C
severe: < 28 C
Hypothermic arrest
- No adrenaline or other drugs until >30C
- Between 30-35C double the dose intervals
- Shock VF up to 3 times if necessary, then no further shocks until T>30C
- ‘Not dead until warm and dead’ (30-32C)
Morbid obesity (RCoA old book)
Airway: short neck, large chin, large thoracic fat, reduced ROM of atlanto-axial joint, fat in pharyngeal wall, tendency to airway collapse and OSA. Higher risk difficult airway.
RS: elevated O2 consumption, low FRC (can encroach on CC), shorter time to apnoeic desaturation, OSA, OHS, pulmonary hypertension, cor pulmonale, reduced compliance, difficult airway, higher PE risk
CVS: higher blood volume/CO/SVR, HTN, high cholesterol, LVH, IHD, CCF, cerebrovascular disease, polycythaemia, VTE
GI: HH, GORD, gallstones, fatty liver
Endo: DM
Pharmacokinetics altered as high fat, low muscle, low TBW. Fat soluble drugs have higher VD (BDZ). Protein binding increased. Renal/hepatic excretion may be reduced. Relative OD if using total weight.
Other: difficult venous access, regional techniques and NIBP cuff fit. Landmarks obscured. Difficult positioning, higher risk of nerve/skin injury.
Postop: delayed recovery, resp depression, LRTI, wound infection, VTE.
62% of UK population are overweight or obese (BMI>25)
25% are obese (BMI>30)
Pulmonary vascular resistance (Mendonca)
- Factors that increase/decrease PVR
- HPV
Factors that increase PVR/HPV: hypoxia (inc altitude), hypercapnoea, acidosis, PEEP, hypothermia, stress, sympathetic stimulation/catecholamines, serotonin, protamine, ketamine, N2O, PGs, increasing alveolar pressure and volume (compression of corner capillaries).
Factors that reduce PVR/HPV: opposite of the above, + nitric oxide, prostacyclin, ACEi, PDE, histamine, volatiles > 1 MAC.
Treat high PVR with: hyperventilation, NO, morphine, GTN/SNP, prostacyclin, aminophylline, CCBs.
Pul vasodilators are used in ARDS.
NO - start at 5ppm, usual range 5-20, max 80. SEs: formation of NO2 which can cause pul oedema, MetHb, reduced plt aggregation.
HPV: PaO2<9 causes reflex vasoconstriction within seconds. Arterioles account for 80%, veins 20%. Improves V/Q matching. Occurs in denervated lungs so not neurally mediated; several theories, likely chemical mediators - endothelin, reduced NO, smooth muscle contraction. It is biphasic (2nd phase after 1h). Active in fetus, and becomes relevant in OLV and lung pathology.
HPV relevant in: OLV, fetal circulation, altitude, ARDS, GA, PHTN
Pre-eclampsia (Mendonca, Krishnachetty)
140/90 and proteinuria PCR>30mg/mmol (or >300mg/24h or two samples of pro 2+ >4h apart) after 20/40 (up to 30% cases postpartum)
Oedema and raised uric acid common but not part of criteria.
5% of all pregnancies a/w eclampsia (1-2%), HELLP, acute fatty liver of preg
RFs: primip, PHx/FHx PET, age <25/>35, multiple pregnancy, GDM, pre-existing HTN/DM/kidney disease, obesity, new partner Probably a genetic predisposition and possibly autoimmune
Pathophys: 1. Abnormal placentation 2. Endothelial dysfunction.
Failure of trophoblastic invasion of spiral arteries –> high resistance vascular bed (low in normal pregnancy) –> placental ischaemia/hypoxia. Immune response is triggered: release of inflammatory mediators, endogenous vasoconstrictors (TXA2), plt aggregation, coagulation cascade activation and fibrin deposition occur.
Result = vasoconstriction, oedema (peripheral, pulmonary, cerebral), end organ hypoperfusion, reduced placental blood flow.
Principles
- BP control
- Early planned delivery; steroids
- Prevent seizures
- Restrictive fluid strategy
Airway: higher risk difficult intubation (facial/tongue oedema; voice changes may signify)
CVS: BP up, SVR up, CO down
RS: pul oedema, airway oedema
CNS: SNS activity up, cerebral oedema, hypertensive encephalopathy, ICH, vasospasm, visual disturbance
Haem: plt activation/consumption, DIC, haemoconcentration
Renal: ischaemia –> GFR down, proteinuria, clearance down
Hepatic: subcapsular haemorrhage, spontaneous rupture, transaminitis and raised bili, reduced drug metabolism
Fetus: IUGR/low birthweight, abruption, mortality
Severe PET: BP>160/110 or additional features e.g. proteinuria >5g/24h, oliguria, cerebral irritability, epigastric/RUQ pain, pulmonary oedema.
Symptoms: malaise, HA, abdo pain, SOB, bruising, oliguria
HELLP: a/w DIC, abruption, hepatic ischaemia and MOF. Presents as AP, N+V.
Eclampsia can occur up to 2/52pp.
Complications: ICH, liver rupture, placental abruption, DIC, heart failure.
Up: soluble endoglin (SEng)
Down: VEGF, PAPP-A
Rx: early diagnosis, BP control, vigilance for eclampsia/prevent seizures, timely delivery, steroids before 34/40 BP: if >150/100 –> labetalol (2nd: methyldopa, nifedipine, hydralazine). MgSO4 prevents progression to eclampsia. Restrictive fluid strategy. Avoid plts. Consider dex 10mg BD to raise plts. Consider PLEX for refractory haemolysis.
Anaes: early epidural, bloods <6h for neuraxial, obtund pressor response if GA
Mg 4-5g load 5m, 1g/h until 24h pp Therapeutic 2-4 mmol/L Loss of reflexes >5 Respiratory depression 6-7 Cardiac arrest >10-12
Cerebral circulation (Mendonca, Krishnachetty)
Cerebral circ affected by head up/down position and bypass.
Factors affecting CBF: pCO2, pO2, CMRO2, CPP, drugs, temperature
Autoregulation: metabolic (H+/K+/lactate/adenosine), myogenic, neurogenic
Mx raised ICP: reduction of blood, brain or CSF
Measurement of CBF
- Transcranial Doppler (MCA)
- Kety-Schmidt technique - applies Fick principle using N2O. Pt breathes 10% N2O for 10m; paired peripheral arterial and jugular venous bulb samples are taken. Speed of equilibration = measure of delivery to brain.
- PET
- SPECT
All volatiles above 1.5 MAC abolisn autoregulation except sevo (where it is preserved up to 2 MAC). Sevo also increases CBF to a lesser extent than other volatiles, so is preferred in neuro.
All induction agents reduce CMRO2 except ketamine. Opiates indirectly increase CBF because resp depression raises CO2.
Cerebral steal: vasodilatation diverts blood away from damaged areas of brain. Inverse steal: inducing vasoconstriction of normal areas may divert blood towards damaged areas of brain (e.g. thiopentone and hypocapnoea).
Weaning from ventilation (Mendonca)
A: patent with protective reflexes
B: FiO2<0.4, PEEP<8, PS<10, spontaneously breathing, VC>15ml/kg, good cough
C: stable on minimal inotropic support
RR<35
D: sufficient LOC
E: original pathology resolve, no procedures in near future
Indices
Max PIP 30, P.01 -4 or more
RSBI<80 - likely success; >105 likely failure (PEEP needs to be 0 to judge)
Other: CROP, IEQ, WI, IWI
SBT: T-piece, CPAP or low level PS for up to 30m. Terminate if RR>35, SpO2<90%, HR>140, arrhythmia, SBP>180 or <90, agitation, sweating, anxiety.
RFs for failure: age>54, chronic cardioresp disease, obesity, neuromuscular disease, +ve FB, vent>6 days
Trache pros: better tolerated, reduced sedation, reduced dead space and WOB, better mouth hygiene, faciliates wean, can potentially talk and eat.
Principles of weaning
- Gradual reductions in support
- Adequate rest periods, especially at night
- ‘Sprints’ where support rapidly reduced for short periods
- Periods of cuff deflation
- Downsizing of trache tube or changing to fenestrated tube
Failure
- infection - BAL, CXR
- cardiac disease - echo,BNP
- metabolic
- ICUAW
- fluid overload
Coagulation cascade (Mendonca)
Cell-based
Initiation: tissue factor exposed
Amplification: platelets and cofactors activated
Propagation: thrombin generated
(Classical: I/E pathways then FCP - X to Xa, prothrombin to thrombin, fibrinogen to fibrin)
Tissue damage –> tissue factor exposed –> makes contact with circulating factor 7 –> forms a complex which triggers cascade by activating factors 9 and 10 –> 10 binds to 2 to form thrombin.
Then amplification - thrombin burst
Propagation - clot formation
Stabilisation - cross-linked fibrin meshwork
Tissue factor = a transmembrane glycoprotein receptor, ubiquitous in body. Also involved in inflammation, atherosclerosis and metastasis.
Fibrinolysis - breakdown of fibrin by plasmin into soluble FDPs (one type of which is D-dimers) which can then be eliminated.
TEDS - graded circumferential pressure - highest at distal portion; increases blood velocity
Heparin may increase tissue factor pathway inhibitor production.
Brainstem death and organ donation (Krishnachetty, past Q as short case in old RCoA book)
BSD changes: occur due to rising ICP then predictable pattern of changes and MOF. CVS - MAP rises to maintain ICP; sympathetic storm - HTN, ECG changes, high SVR, myocardial ischaemia, reflex bradycardia (Cushing). Herniation/coning –> loss of spinal cord sympathetic activity, vasodilatation, low CO. Pituitary ischaemia causes cranial DI. Hypothalamic ischaemia causes loss of thermoregulation. Dying brain releases tissue factor –> coagulopathy.
BSD: irreversible loss of all brain functions. Coma, apnoea, absence of brainstem reflexes.
Preconditions: irreversible brain damage of known aetiology, coma off all sedation/analgesia/paralysis, apnoea, absence of mitigating factors (T>35, MAP>60, absence of severe metabolic/electrolyte disturbance), ability to do BST (no severe oxygenation problem or high C spine injury, at least one eye and ear). Test at least 6h after loss of last reflex.
Red flag conditions: neuromuscular, prolonged fentanyl infusion, posterior fossa pathology.
BST: GCS 3, pupils fixed/unreactive (CN II, III), corneal reflex (CN V, VII), oculo-vestibular reflexes (CN III, IV, VI, VIII), gag (CN IX, X), cough (CN X), positive apnoea test (after preoxygenation, starting PaCO2>6 and rise to 6.65). 1/11/12 not tested. Excluded from BST: babies <2/12.
Ancillary tests: 4 vessel angiography, radionuclide imaging, CTA.
Organ donation: SNOD ref, check ODR, approach NOK. Specific organ testing, tissue typing, viral screening.
CI: absolute (prion disease and AIDS), relative (disseminated ca, age>70, active TB)
Organ specific criteria: heart/lung >65, chronic disease e.g. IHD, cirrhosis, ESRF, IDDM or previous malignancy of that organ.
Care of the donor
General ICU measures (feeding, abx, turning, electrolytes, insulin/glu 4-10, VTE, warming/T36-37.5, correct coagulation).
CVS: fluids, vasopressin (+/- steroids to reduce inotrope req), short acting drugs during catecholamine storm e.g. GTN, esmolol. HR 60-120, MAP60-80, CI>2.1, ScvO2>60%
RS: LTVV, methylpred 15mg/kg, PaO2>10, FiO2<0.4 as able, PaCO2 5-6.5 (or higher provided pH>7.25), recruitment manouvres, suctioning, physio
Endo: consider T3, desmopressin, insulin
Renal: avoid fluid overload, match polyuric losses, UO 0.5-2ml/kg/h
Most common disturbances in BSD: hypotension (81%), DI (65%), DIC (28%), arrhythmia (25%), pul oedema (18%), metabolic acidosis (11%)
Apnoeic oxygenation (Krishnachetty, past Q)
VO2 continues at 250ml/min - this volume continues to cross the alveoli. Only up to 20ml/min CO2 diffuses out (rest is buffered), so net 230ml in/min which creates subatmospheric pressure. If airway patent, more gas is drawn down from pharynx without any activity from diaphragm or lung expansion. Nasal cannulae can create an O2 reservoir in pharynx. Apnoeic oxygenation (mass transfer of O2) can be maintained for 100m in healthy pts as an O2 deficit of only 20ml/min occurs. Technique limited by CO2 buildup and acidosis, and dependent on airway patency.
Factors influencing time to apnoeic desaturation:
- Reservoir (pre-O2, FRC)
- Rate of use (higher in children, critical illness)
- Duration of apnoea
- Hb
- Airway patency (loss –> atelectasis)
Pre-O2
If FRC 2.5L, at FiO2 0.21, O2 reservoir is about 500ml (2 mins’ worth). If de-nitrogenated, 2.5L O2 = 10 mins’ worth.
Liver disease (Krishnachetty, past Q)
ALF: absence of chronic liver disease, +
- encephalopathy
- jaundice
- coagulopathy
Mx ALF
- treat cause, supportive
- ammonia removal with lactulose, LOLA (L-ornithine L-arginine), phosphate enemas, branch chain amino acids, RRT (do not avoid feeding/protein - doesn’t help and precipitates sarcopenia)
- treat/anticipate cerebral oedema - maximise CPP, Na high-normal; ICP monitoring controversial
- avoid treating coagulopathy (beyond vit K) unless bleeding, as affects transplant decisions
- search for and treat sepsis
Tests of liver function: enzymatic, synthetic
Decompensation: sepsis, GI bleed, electrolyte dist, excess protein
Pathophysiology of liver disease: steatosis, hepatitis, cirrhosis.
O/E: peripheral stigmata, EJAC, portal HTN, poor nutrition
Hepatorenal syn: renal imp a/w liver disease (diagnosis of exclusion). Type 1 - rapid, severe. Type 2 - slow, progressive.
Preop - fluid/nutrition/electrolytes/coagulopathy, consider paracentesis, antacids
Intraop - increased sensitivity/reduced drug clearance, increased Vd, altered PPB, caution with neuraxial, invasive monitoring, abx, glycaemic control
Postop - ICU
Ammonia normally detox to ammonium by liver, then renally excreted
In liver disease, ammonia is turned into glutamine in brain; this causes mitochondrial dysfunction, astrocyte swelling and resultant cerebral oedema and raised ICP. >100 = severe encephalopathy. >200 = raised ICP
Denervated heart (Krishnachetty, Mendonca, past Q)
Heart innervation: PNS from vagus, SNS from T1-4 cardioaccelerator fibres. SNS = positive chronotropy, inotropy and dromotropy (electrical conductivity across AVN). PNS opposite. Deep and superficial cardiac plexi innervate atria and ventricles.
Ind: end stage heart disease e.g. congenital, CM, valvular. Also combined lung/heart for lung disease impacting heart.
Criteria: imp LV, NYHA 3/4, on optimal medical tx, CRT done if indicated, evidence of poor prognosis (e.g. high BNP, VO2 max <12 on BB, poor prognosis on Heart Failure Survival Score).
CI: PHTN, irreversible end organ damage (lung/liver/kidney), DM with end organ damage, active smoking/alcohol/substance misuse.
90% 1y survival, 50% at 10y.
Denervated heart: no SNS/PNS innervation (some SNS might restart 1y post tx). Resting HR 90-110. Poor response to hypovolaemia - cannot increase HR. No response to drugs acting via ANS e.g. atropine, glyco, digoxin. No response to baroreceptors/CSM, Valsalva, light anaesthesia or pain. No pressor response to laryngoscopy/intubation. No ischaemic pain - need regular angiograms. Need to maintain preload. Sensitive to catecholamines; reduced response to ephedrine as lower stores of NA in myocardial neurones. Still use glyco with neo for reversal as counteracts peripheral effects e.g. nausea/salivation/bronchospasm.
Anaes concerns: denervation issues, original pathology, accelerated atherosclerosis/silent ischaemia, likely to have PPM/ICD, difficult vascular access (avoid RIJ - endomyocardial biopsy route), immunosuppression and drug SEs (need CMV -ve irradiated blood, abx, strict asepsis, steroid supplementation, drug levels, renal dysfunction - avoid NSAIDs), extensive workup/intraop monitoring needed.
Rejection: acute (first 3/12), chronic (allograft vasculopathy - reduced by statins, leading cause of late death).
Immunosuppressants: SCAT
Ventilator associated pneumonia (Krishnachetty, past Q)
Clinical diagnosis >48h IPPV (NICE). Most common hospital acquired infection in ICU - up to 28% of pts, peak at 5 days. Mortality up to 50%.
Features: fever, purulent secretions, worsening gas exchange, rising inflammatory markers, new pul infiltrates on CXR, growth of an org.
Clinical Pulmonary Infection Score: clinical, physiological, micro and radiographic evidence added - score 0-12, 6 or more = VAP but low sens/spec.
Orgs: mainly Gram -ves overall. Early: Strep pneumoniae, H.influenzae, MSSA, Gram -ve bacilli, E.coli, Klebsiella, Enterobacter, Proteus, Serratia. Late: drug-resistant orgs - MRSA, Acinetobacter, Pseudomonas, ESBL.
RFs: pt factors (age, COPD/lung disease, ARDS, low albumin, impaired LOC, trauma, burns, URT colonisation, high aspirates), intervention factors (duration of MV, level of sedation, NMBs, antacids/PPI/H2Bs, NGT, supine, frequent circuit changes, transfer outside ICU).
Path: URT colonisation –> infected secretions enter distal bronchi around ETT cuff, via suction catheter, vent tubing. ICU pts often immunosuppressed, have natural barriers breached and impaired protective reflexes.
Prevention: general (handwashing, sterile equipment, barrier nursing/universal precautions, reducing unnecessary contact).
Specific
* Reducing colonisation (chlorhex mouthwash, SDD (but risk of C.diff, abx resistance)
* Reducing aspiration (head up, subglottic suctioning, cuff pressure >20)
* Early liberation from MV (early trache, sedation holds)
* Choice of GI drugs (?H2B over PPI, stopping when on full feed)
Pulmonary hypertension (Krishnachetty)
PH = MPAP>25mmHg at rest (>35 mod, >50 severe)
Exertional dyspnoea, lethargy, fatigue, syncope - vague sx, often delayed dx
Signs: PR/TR murmur, high JVP with V waves (TR), hepatomegaly, ascites, oedema, fixed/split S2.
ECG: RAH, RAD, RVH, ST dep/TWI. Echo determines systolic pul pressure and diagnoses CHD, valve disorders etc. Gold standard cardiac catheter. CPET, VTE scans. CXR: RAH/RVH, bulky hila, oligaemic lung fields, Kerley B lines.
WHO classification: group 1-5 according to aetiology. Group 1 is PAH (arterial), 2-5 are PH (venous; heart/lung/VTE/unclear respectively).
Path: hypertrophy and intimal fibrosis of pulmonary vasculature –> vessel narrowing and increased pressures. RVF occurs when MPAP>50. LVF can then ensue as reduced venous return and septal interdependence.
Rx: general, medical, surgical. Treat underlying cause, exercise. Medical: O2, prostacyclin agonists (epoprostenol), NO-CGMP enhancers (sildenafil), endothelin antagonists (bosentan), CCBs, NO (for reactivity testing), digoxin, diuretics, anticoagulation. Surgical: lung transplantation, atrial septostomy.
Anaes: all induction/NMB drugs ok except ketamine (increases PVR). Avoid N2O. Invasive BP, CVC, CO/PAFC. Aims: full, slow, tight. Avoid dropping SVR - caution with neuraxial. Avoid increased PVR, myocardial depression and arrhythmias.
Immune response (past Q)
Barrier, innate, acquired Cellular/humoral What are antibodies IgA/D/E/G/M Monoclonal abs - what are they When do we give IVIG
Nutrition and starvation, refeeding syndrome (past Q, Krishnachetty)
Carbohydrate 4g/kg (as 50% dextrose; should provide 60% of non-protein calories)
Protein 1.5g/kg (as 10% amino acid solution)
Fat 1g/kg (as 10% lipid emulsion; up to 40% of non-protein calories)
H2O 30 ml/kg/day (or 2ml/kg/h) + losses
Na+ 1-2 mmol/kg Cl- 1-2 mmol/kg K+ 1 mmol/kg Ca2+ 0.1 mmol/kg Mg2+ 0.1 mmol/kg PO4 0.4 mmol/kg (Electrolytes guided by plasma levels) Nitrogen 14g
Vitamins: B complex, folate, vit C, vit E, B12, ADEK
Trace elements: Fe, Zn, Se, Cu, I, Mn, Cr
Other: glutamine (trauma/burns), L-arginine (elective surgery), omega 3 (ARDS)
Critical illness increases BMR by about 40%. Catabolism cannot be switched off –> risk of overfeeding, known to be deleterious. Survival is best in pts receiving 1/3 to 2/3 estimated nutritional needs (compared to <1/3 or >2/3 - Krishnan et al 2003). Start at 10kCal/kg/day if at risk of refeeding syndrome.
(1kCal = 4.19J; 1g glucose = 4kCal)
EN within 24-48h if unlikely to eat for 3-5d. PN - ESPEN 24-48h, ASPEN 7d.
Malnutrition leads to increased vent days, LoS, infections, delayed wound healing and delayed mobilisation.
Starvation
1st 24h - glycogenolysis, gluconeogenesis
72h - ketogenesis, lipolysis
Weeks - proteolysis
Ax nutritional status
- MUST, hx/ex
- Bedside: ketones, glu, ABG
- Lab: electrolytes, alb, liver synthetic, vitamins/minerals
- Advanced: indirect calorimetry, anthropomorphic, nitrogen balance
EN - cheaper/simpler/preserves gut function/less ulceration but aspiration/VAP/sepsis, diarrhoea, NG risks.
PN - no asp risk but CVC risks, refeeding syn, electrolyte dist, cost, interruptions, liver dys, hyperglycaemia, hyperchloraemic met acid (from Cl in AAs)
Smoking (past Q)
COHb
Cherry red - supermarket meat!
RS: COHb reduces Hb for O2 carriage, shifts curve left, CO inhibits cytochrome oxidase (needed for aerobic metabolism), airway irritability, coughing/breathholding/laryngospasm, impaired mucociliary clearance, high risk postop LRTI, COPD, ca
CVS: HTN, IHD, AAA, CVD, PVD, higher resting catecholamines so increased SNS response to desflurane, periop MI risk
Haem: polycythaemia and VTE risk
GI: GORD, PUD
Cessation 1y: risk of ca/COPD etc declines 6/12: postop complications less 1/12: possible less postop LRTI 1/52: reduced airway irritability 12-24h: clearance of CO
Thyroid (past Q, Mendonca)
Myxoedema - 300-500mcg T4 IV loading dose then 50-100mcg IV OD. Mortality 20-65%. IV steroids until can exclude co-existent Addison’s (dex will not interfere with synacthen). Supportive. Treat cause.
Hyper: Graves’, toxic multinodular goitre, solitary adenoma. Hypo: Hashimoto’s, post radio/surgical.
Preop: FBC (agranulocytosis from tx), ensure clinically and biochemically euthyroid (TFT), any other autoimmune disease, degree of airway compromise/retrosternal extension (CXR/thoracic inlet AP/lateral/CT/nasendoscopy). Stridor/dysphonia/orthopnoea suggest risk of airway compromise on induction.
Intraop: GA vs RA/LA (cervical plexus + midline SC infiltration) +/- sedation. Gas induction (may be prolonged in obstruction) vs. AFOI vs. awake trache. If stridor present, avoid AFOI (cork in bottle). Spray cords so less pressor response and to surgical manipulation. RLN monitoring tube (–> remi, no MR), reinforced, taped, protect eyes, head up, bolster between shoulders. Dex. Valsalva at end for haemostasis. Reverse. Leak test. Awake extubation vs. deep with LMA exchange.
Postop problems: haemorrhage and airway compromise, laryngeal oedema, RLN palsy, hypocalcaemia, tracheomalacia, thyroid storm, PTX.
RLN monitoring: special ETT has EMG electrode to detect vocal cord movement. Electrodes have to be in contact with vocal cords.
Dietary iodide –> oxidised to iodine in thyroid follicular cells by thyroid peroxidase –> iodine iodinates tyrosine residues –> MIT and DIT formed –> combine to make T3 and T4, stored bound to thyroglobulin in colloid –> endocytosed and cleaved when stimulated by TSH. Carbimazole prevents iodide oxidation. PTU prevents iodination of tyrosine and peripheral conversion of T4 to T3.
Thyroid storm: cold fluids, antipyretics, PTU then Lugol’s iodine (prevents further release of thyroid hormones), beta blockers, steroids. Consider plasma exchange and dantrolene. Mortality rate 10-30%. Hypermetabolic state, excess catecholamines, high O2 consumption. Avoid salicylates as can displace T4 from TBG.
Respiratory function tests
Spirometry
Flow volume loops
DLCO (=TLCO)
High: polycythaemia, pulmonary haemorrhage, asthma, L to R shunt
Low: emphysema, CO-Hb (inc. smoking), CF, bronchiectasis, ILD, heart failure, pulmonary arterial HTN, anaemia
RV should not be more than a third of TLC
Asthma has reversibility >12%
LTOT
PaO2 <7.3 on 2 occasions 3 weeks apart
Or <8 with polycythaemia/cor pulmonale
Prone positioning (past Q)
Indications - surgical (spine, Achilles, pilonidal), SRF/ARDS
Reinforced tube
Simple prone vs. tuck
Min 6 ppl (airway, feet, +2 each side; 1 to be the surgeon)
Procedure: bed to table, secure lines/tape ETT/protect eyes etc first, disconnect, ABC (ETT may become endobronchial), top to toe, ABC, surgery start
CVS: CO falls, mainly due to lower SV from reduced preload (IVC compression)
RS: FRC/PaO2 rise, better V/Q matching
Injuries: MSK (pressure sores, dislocation e.g. joint replacements, compartment syndrome/rhabdo), nerves (SOF, brachial plexus, ulnar, lat cut nerve of thigh), ocular (direct pressure or underperfusion), abdominal (compartment syndrome, organ ischaemia, pancreatitis), airway (tongue/mouth swelling)
Montreal mattress (hole for abdo)/wedge under chest/pelvis - decrease abdo pressure
How it works in ARDS
- Reduces ventral-dorsal transpulmonary pressure difference (recruits collapsed dorsal alveoli)
- Reduces dorsal lung compression (by heart and diaphragm)
- Improves lung perfusion (previously dependent areas retain highest blood flow)
- Might increase FRC, reduce EVLW and improve secretion drainage
Other reasons to prone - posterior burns/wounds/surgery
CI: raised ICP, recent surgery, spinal instability, pregnancy, CVS instability
Procedure: assemble/brief team, secure lines/tubes, disconnect non essentials, empty stomach, pre-O2, turn, recheck ABCs
Diabetes
What happens in DKA? No insulin, so glucose cannot enter cells. Metabolism switches from carbohydrate to fats (as per starvation). FFAs are broken down into ketoacids by liver, hence rise in ketone bodies. Stress hormones rise and exacerbate the hyperglycaemia by glycogenolysis and gluconeogenesis. The hyperglycaemia causes an osmotic diuresis and electrolyte imbalance, exacerbated further by vomiting.
Main causes of death in DKA = K+ disturbance, cerebral oedema and aspiration due to low GCS. Other comps: iatrogenic pul oedema, hypoglycaemia.
Prevalence of DM = 9%! 90% of which is type 2. Increases with age (24% of >75s). Male preponderance.
Markers of severe DKA: pH<7, HCO3<5, Ket>6, SBP<90, GCS<12, SpO2<92, anion gap>16.
Typical deficits in DKA: water 100ml/kg, K 3-5mmol/kg, Na 7-10mmol/kg.
In HHS, enough insulin sensitivity to inhibit ketogenesis but cannot increase glu uptake. In DKA, can’t do either. HHS involves less aggressive fluid replacement due to risk of cerebral oedema.
Joint British Diabetes Societies - DKA targets
- Ketone fall 0.5mmol/L/h
- Glucose fall 3mmol/L/h
- Bicarb rise 3mmol/L/h
- K+ kept 4-5.5
Ketonaemia and acidosis should have resolved by 24h.
0.1u/kg/h FRII until ket <0.3mmol/L
Give normal long acting insulin
If K 3.5-5.5, 40mmol in each bag. Above 5.5 nil, below 3.5 likely need central replacement
When glu <14, add in 10% dex 125ml/h
Fluid regime stat/1/2/2/4/4/6 should not be used in young/pregnant (cerebral oedema), elderly/hepatic/renal failure (fluid overload)
Identify and treat precipitants
Specialist diabetic review
Fluids in paediatrics/hyponatraemia (past Q)
4-2-1 rule
5% dex with 0.45% saline for maintenance (half saline as kidneys immature, cannot handle Na load)
CSL for replacement
Serum bicarb <17 is sensitive for moderate-severe hypovolaemia
Pancreatitis (past Q)
10-20% is severe
IAP criteria for diagnosis
Ranson for prognosis
Glasgow, Atlanta and Balthazar for severity
Gallstones, EtOH, ERCP, trauma, drugs (aza, diuretics, steroids), metabolic (lipids), infections (mycoplasma, CMV)
US abdo first; CT only after 72h if not improving (15% are necrotic)
Occasionally FNA
ERCP e.g. if cholangitis
Functions of pancreas
- Exocrine
Production of digestive enzymes - amylase, lipase, proteases
- Endocrine
Production of endogenous hormones that regulate glycaemic control (alpha - glucagon, beta - insulin, gamma - pancreatic polypeptide, delta - somatostatin)
What is a pseudocyst? Encapsulated body of fluid within the pancreas. Looks like a cyst on imaging but absence of epithelialized wall.
Tx
Largely supportive
Fluids
Feed
Abx not indicated unless ev of infection
If infected necrosis: abx + perc drainage or delayed open necrosectomy
Comps
Local: necrosis (sterile/infected), pseudocyst, abscess, pseudoaneurysm, mesenteric vein thrombosis, abdo compartment syn
Systemic: ARDS, AKI, shock, MOF
Anaemia (past Q, Krishnachetty)
Microcytic anaemia
- Iron deficiency
- Chronic blood loss
- Bone marrow failure e.g. haem malignancy
- Malabsorption
- SCD, thalassaemia
Macro: B12 or folate deficiency, hypothyroidism, alcoholism, chemo, anticonvulsants
Normo: blood loss, dilutional, BM failure, Addisonian, renal/liver disease
Options:
- Proceed with surgery regardless (higher periop risk MACE)
- Transfuse (concerns over allogenic transfusion and cancer recurrence, higher postop complications and mortality in retrospective data) - only if symptomatic (angina, dyspnoea, failure)
- Iron replacement PO or IV (latter ideal)
TRICC study - Hb 7 vs 9, no mortality difference
Sodium homeostasis (past Q)
DI - central/nephrogenic. Urine >3L/day. High serum Na+>145 and serum osm >300mOsm/kg. Urine osm <300mOsm/kg. Rx DDAVP for central, water replacement and thiazides for nephrogenic.
SIADH - serum Na+<135, serum osm <280mOsm/kg, low urine Na+, high urine osm. Rx water restriction, hypertonic saline, diuretics, vaptans (ADH receptor antgonists). ADH causes water resorption via insertion of aquaporins into CD mems.
SIADH and CSW both have low serum Na, high urine Na and concentrated urine. The key to differentiation is fluid status. In SIADH pts are eu- or hypervolaemic; in CSW they are hypovolaemic. Important to tell difference as tx differs.
SIADH = fluid restriction, demeclocycline, vaptans CSW = Na replacement, fludrocortisone
Spinal cord injury and autonomic dysreflexia (past Q, Krishnachetty)
Commonest C-spine # = C4-6. Most fatal ones C1/2.
Spinal shock: initial phase of flaccidity, areflexia, loss of sphincter tone, priaprism. Lasts hours-weeks. Not a true form of shock as it is neurological, not cardiovascular.
Neurogenic shock: hypotension, paradoxical bradycardia, vasodilatation. Due to SNS damage from lesions above T6. Above T4, cardiac sympathetic supply is also lost.
Anaes concerns post SCI: difficult airway (MILS and retropharyngeal haematoma), AD/labile BP, severe brady on tracheal suctioning/laryngoscopy, sux hyperkalaemia, aspiration risk, latex sensitivity. Art line, temp monitor, urinary catheter.
Autonomic dysreflexia/hyperreflexia refers to a small stimulus below the level of a spinal cord lesion resulting in an exaggerated autonomic response. Occurs 3/52 to 9/12 post injury in lesions above T6 (91% in complete injury, 27% in incomplete injury). Triggered by surgical stimuli, bladder/bowel distension. Results in vasoconstriction below injury and severe HTN - risk of SAH and seizures. Below injury - SNS predominant; pale, cold skin. Above injury - PNS predominant; flushed skin, reflex bradycardia. Mechanism not fully known - possibly alpha receptors become hyper-responsive due to low resting catecholamine levels. Possibly also loss of descending inhibition. Rx: short-acting drugs e.g. GTN, remi, labetalol, volatiles. Very high levels of NA and A are seen during episodes.
Why T6? This level controls autonomic supply to largest blood reservoir - the splanchnic circulation. Above T6, SNS activation is uninhibited. Below T6, the PNS counteracts to prevent HTN.
SCI: 40-50% colonised with multi-drug resistant organisms. Often ESBL Gram negatives associated with urinary catheters. Also MRSA, VRE.
Other chronic issues
- latex allergy
- org colonisation - MDRs
- VTE
- pressure sores
- if worsening neurology - consider syrinx
- psychological
Burns (past Q)
Inhalational injury: supraglottic, tracheobronchial, parenchymal. Singed nasal hair/eyebrows/eyelashes, hoarse voice, stridor, carbonaceous sputum, enclosed space/delayed escape, toxic substances burned
Inhalational injury increases mortality by 20% and pneumonia by 40%
Intubate early, uncut tube, may need smaller
Humidification, PT, bronch + BAL daily, nebs inc heparin/NAC/salbutamol, protective ventilation, fluid balance
Sux ok first 24h
Full thickness circumferential chest burns can impede ventilation
Parkland formula
Rule of 9s (for children, head is 18%)
Monitoring problems: ECG electrodes may not stick, use SC needle electrodes; CO poisoning - SpO2 may over-read; NIBP over damaged skin - art line.
Baux score: %BSA x age (+17 if inhalational injury). >140 considered unsurvivable
ICU problems: infection, fluid loss/creep, temperature control, nutrition.
Severe burns: age<5 or >60, >15% TBSA adults or >10% children, full thickness, smoke inhalation (esp severe acidosis, failure to raise core temp, COHb>10%)
Aim MAP>60 only, don’t aim for normal filling pressures
Target UOP 0.5ml/kg/h
HR<110 usually indicates adequate filling
Consider colloid (HAS/FFP) to maintain plasma oncotic pressure and prevent further fluid extravasation
Fluid creep - risk of limb/abdo compartment syn, ocular HTN, resp failure. Need for decompressive laparotomy = mortality 88-100%.
Sepsis v hard to judge clinically and biochemically; higher fluid reqs, falling plts, altered GCS, worsening renal/pulmonary function.
Catabolism - nutrition, wound coverage, prevent sepsis, warm environment, resistive exercise, oxandrolone (anabolic steroid), propranolol.
Burn shock
Neb heparin
Glutamine
Aortic stenosis (past Q)
Aims: SR, full, slow, tight
Avoid drugs that reduce preload (diuretics, vasodilators); keep BP at pre-anaesthetic values
AS affects 2% of over 65s
Normal: mean gradient <5mmHg, area 3-4cm2, pgrad <10
Mild: mgrad <25, area >1.2, pgrad <40
Moderate: mgrad 25-40, area 0.8-1.2, pgrad 40-65
Severe: mgrad 40-50, area 0.6-0.8, pgrad >65
Critical: mgrad >50, area <0.6
Onset of symptoms = 25% 1y mortality, >50% at 2y. Asymptomatic: <1% mortality/yr
Gradient can be misleading if poor LV (low flow, low gradient AS)
Rx balloon valvuloplasty, AVR, TAVI (latter done in hybrid angio suite with bypass machine/perfusionist on standby; transvascular or transapical approach)
Gradient is calculated by modified Bernoulli equation from jet velocity. Pressure gradient underestimates severity when LV is poor.
Pyloric stenosis (Mendonca)
3 in 1000, M:F 4:1, 3-5/52 age, hypochloraemic, hypokalaemic, hyponatraemic metabolic alkalosis. Alkaline urine then paradoxical aciduriaFluid loss in children: mild (5%), mod (10), severe (15). Fontanelle, turgor, MMs, eyes, HR, RR, UO Isotonic boluses then saline/dex maintenance with K once PU’ing NGT and replace losses with saline 4-2-1 fluid rule RSI. Paracet, LA, reversal, awake extubation, HDU, O2 postop, apnoea monitor, fluids to prevent hypoglycaemia Child vs. adult differences
SVCO (past Q)
Impaired venous return through the SVC to RA. Causes obstruction of venous flow from upper half of body.
Major SVC collateral is the azygous vein - if obstruction distal to azygous insertion, compensation occurs. If proximal flow must bypass the SVC and return via the internal mammary, superficial thoracoabdominal, vertebral venous system to the ICV, resulting in very high pressures.
Causes: intrinsic (thrombus e.g. from CVC) or extrinsic (ca, retrosternal goitre, lymphadenopathy).
Features: upper body oedema/plethora, cough, dyspnoea, syncope, HA, CP, nasal stuffiness.
O/E: plethoric/cyanosed/oedematous, conjunctival inj, exophthalmos, CVC scars, distended non-pulsatile neck veins, stridor, Horner’s, hoarseness, chest collaterals, pleural effusions, cardiac tamponade, Pemberton’s sign (bilateral arm elevation causes facial plethora and dyspnoea - thoracic inlet obstruction).
Rx: treat cause e.g. chemo, stenting/anticoagulation.
Anaes implications: difficult airway, supplemental O2, IV access in IVC territory, induction sat up, airway oedema/friability, RLN palsy, reduced venous return –> CVS instability.
Cervical LN bx: LA, cervical plexus block, GA. CPB on standby. Avoid GA, PPV, MRs, coughing. Induce sat up, preferably inhalational, keep SV, use LMA. If need ETT, AFOI with uncut ETT of smaller calibre. Maintenance with volatile, or TIVA.
Emergence: risk of obstruction due to oedema, bleeding, tracheomalacia. Extubate awake and sat up in ICU. Perform leak test, give dex, adrenaline nebs, consider extubating over airway exchange catheter. Full airway kit inc difficult airway trolley available.
Obstruction following gas induction: follow DAS guidelines, although mindful that Plan D will not bypass obstruction if intrathoracic.
Simple measures: attempt to intubate (may need small tube/MLT), optimise position (sit up, lateral), deliberate endobronchial intubation, exclude equipment problem (if can squeeze bag off the pt, the circuit is patent)
Advanced techniques: fibreoptic, rigid bronch (dilatation/laser/stent), jet vent, CPB/ECMO as rescue
Reducing tumour size: steroids, chemo/radiotx, endoscopic debulking
Pituitary disorders
Acromegaly
SIADH
DI
Cystic fibrosis
Delta F508 chromosome 7, aut rec
1 in 2500 births, carrier 1 in 29
Abnormal CFTR protein –> Cl- trapping in cells –> Na+ movement into cells to neutralise potential across membrane –> excess salt in sweat, thick tenacious secretions
Recurrent LRTI, bronchiectasis, PHTN, cor pulmonale
Pancreas, GIT, liver involvement, male infertility, female subfertility
Sweat test and genotyping for diagnosis
Acromegaly
GH excess (before puberty = gigantism). 6-8/million. Airway - difficult, MP falsely reassuring, laryngeal stenosis, hoarseness/RLN palsy, do indirect laryngoscopy (nasendoscopy/mirror/VL) consider AFOI/awake trache. OSA, obstructive spirometry, HTN, IHD, CM, DM, CN palsies, raised ICP, venous sinus thrombosis, ca colon. Random GH/IGF-1 suggestive, OGTT diagnostic for acromegaly and DM simultaneously. MRI to view extent of tumour. Rx surgical; octreotide may shrink tumour preop; radiotx.
Disorders of red cell morphology (past Q)
Production problem - Thalassaemia - Myelodysplasia - Aplastic anaemia Destruction problem - Haemoglobinopathy - Enzymopathy (G6PD) - Autoimmune - Membrane disorder (spherocytosis)
SCD: avoid oxidant drugs (prilocaine, vit K, aspirin, SNP, penicillin, antimalarials - cause haemolysis).
Sickling occurs at SpO2 85% (PaO2 5.5) in HbSS, 40%/3.5 in HbAS.
HbAS = 40% HbS. HbSS = 90% HbS. Sickledex detects >10% HbS. HbS-beta+ thal is better, HbS-beta0 thal worse.
Hypoxia causes polymerisation of Hb, forming large crystal aggregates called tactoids, which deform RBCs into sickle shape.
Keep Hb>10 (just as effective as exchange transfusion down to HbS<30%).
Chronic anaemia and high 23DPG cause R shift in SCD.
RBC = 6-8microns.
Spherocytosis - aut dom. Problem with RBC membrane protein formation. Spherical cells which are osmotically fragile. Haemolytic anaemia. Tx folate, transfusion, splenectomy.
G6PD - X-linked. Glucose-6-phosphate dehydrogenase converts G6P to 6-phosphogluconate and produces NAPDH, which protects cells against oxidative stress. Haemolysis is triggered by infection, fava beans, oxidant drugs, surgery. Avoid precipitants, give folate, rarely transfuse.
Eisenmenger’s syndrome (past Q)
The syndrome that results from reversal of flow through an intracardiac communication, leading to pulmonary hypertension and cyanosis. Represents irreversible PHTN (unresponsive to 100% O2 or NO - inoperable). Communication can be congenital or acquired (e.g. palliative procedure).
Sx: dyspnoea, poor ex tol, syncope, CP, stroke, brain abscess, cyanosis, CCF, dysrhythmia, hyperviscosity, haemoptysis/pul haemorrhage, endocarditis, sudden death.
Fatal eventually, usually by age 30. Poor QoL due to poor ex tol. 50% mortality if become pregnant.
Fluid deficit
Can be estimated if pre and post deficit weights are known.
In DKA, average deficit is 6L.
In children, mild deficit/dehydration is 5% weight loss, moderate 10% and severe 15%. Can be estimated clinically using fontanelle, skin turgor, mucous membranes, eyes (sunken), HR, RR and UO. Each % deficit can be expressed as % of body weight.
Airway obstruction
- Differentials
- Mx
Intrinsic
- Infection - bacterial (epiglottitis, diphtheria) or viral (influenza, croup)
- Foreign body
- Vocal cord pathology e.g. nerve palsy, mass lesion, laryngospasm
- Angioedema/anaphylaxis
- Low GCS
- Burns/smoke inhalation
- Tracheomalacia, tracheal stenosis
Extrinsic
- Goitre
- Trauma
- Haematoma
Mx:
- Supraglottic/laryngeal - inhalational induction/AFOI/awake trache/TIVA+jet vent/ventilating bronchoscope. For MLB will need to be paralysed. Spray cords with LA. If obstructs during (cork in bottle), immediate trache or single attempt at rigid bronchoscopy.
- Subglottic - tracheal collapse may follow muscle relaxation. If getting below lesion unlikely, need rigid bronch and bypass/ECMO on standby.
ICU weakness
Differential diagnosis
- Brain (vascular, SOL, encephalopathy)
- Brainstem (pontine stroke)
- Spinal cord (compression by tumour/abscess/bleed, transverse myelitis, ischaemia, infection, MND)
- Peripheral nerves (GBS, critical illness polyneuropathy, LEMS, uraemia)
- NMJ (MG, botulism, MRs)
- Muscle fibre (critical illness myopathy, steroid myopathy, electrolyte derangement, disuse atrophy)
–
Diagnosis of exclusion
Under-diagnosed
Affects 25-80% of critically ill patients; 90% of those with ICU LoS>28 days will still have an abnormal EMG 5y later.
Symmetrical motor deficit sparing the face, diminished reflexes, 50% have sensory deficit
Mechanism poorly understood - probably combo of microcirculatory damage, direct neurotoxicity and cytokine-mediated injury
RFs: sepsis, steroids, MRs, hyperglycaemia, immobility, electrolyte disturbance
EMG: reduced action potential with normal conduction velocity
Muscle bx: reduced actin:myosin ratio.
70% make a full recovery.
Prevention: tx sepsis, glycaemic control, minimise steroids/MRs/sedatives, PT, nutrition.
SAH (past Q)
80% due to ruptured aneurysm, 95% of which are in anterior CoW
Sudden onset worst ever HA, vomiting, meningism, altered GCS, focal neurology
DD migraine, tension HA, stroke
RFs: smoking, HTN, alcohol, illicit drugs, pregnancy, female, age 40-60, CTDs, polycystic kidneys.
Diagnosis: CT, LP (OP/xanthochromia) >6h if CT neg, CTA/MRI/direct angiography, transcranial Doppler (for vasospasm).
Tx Neuroprotection SBP<140 unprotected - BBs first line Nimodipine 60mg 4hrly 3/52 TXA before coiling reduces rebleed Coiling>clipping
Coils - cheaper, less invasive, less vasospasm, need anticoag, IR, some not amenable
Clips - best for wide-necked, open procedure with higher M+M
Anaes goals: prevent aneurysm rupture, maintain CPP and cerebral oxygenation, smooth and rapid emergence.
Comps
- Intracranial: rebleed (30%, high mortality), vasospasm/DCI (70% but only sx in 30%; day 4-10; nimodipine reduces by 1/3), hydrocephalus, cerebral oedema, seizures, focal neurology/cranial nerve palsy
- Extra-cranial: myocardial ischaemia and ECG changes due to sympathetic storm, electrolyte disturbance (SIADH, CSW)
Monitoring for DCI
- Clinical
- DSA - gold standard
- CTA
- TCD - MCA velocity >200cm/s or Lindegaard ratio MCA:ECA >3 predicts DCI
Mx DCI
- Induced hypertension (post securing aneurysm)
- Hydration (euvolaemia)
- Intra-arterial nimodipine
- Balloon angioplasty
Options to obtund pressor response: remi 0.5mcg/kg/alfent/fent, esmolol 0.5mg/kg 30s prior, lidocaine 1.5mg/kg, checking neuromuscular block before laryngoscopy.
Preop: Group + save, CTH/angio, stop aspirin.
Intraop: art line, temp probe, UO, maybe CVC, 2 large bore cannulae. Remi (bolus 0.5mcg/kg then infusion 0.25-0.5mcg/kg/min or TCI 3-8ng/ml), titrated propofol, NMDR, ETT. Maintenance TIVA prop/remi or volatile + remi. Avoid N2O (VAE and increases ICP). NOT for hypotensive anaesthesia as decreases CPP (injured brain will not autoregulate). Dex 8-10mg for cerebral oedema. Consider prophylactic anticonvulsant.
Postop: wake up if aneurysm secured and no comps. Keep BP to within 20% of pt’s normal. Neuro obs. Paracet and codeine +/- morphine.
Myotonic dystrophy (past Q)
Myotonia - impaired relaxation
Dystrophy - weakness and atrophy
Aut dom, chr19, prev 1 in 8000
Abnormal Na/Cl channels –> muscles hyperexcitable
2 subtypes - early/severe and late/milder
Conduction defects/CM, autonomic dysfunction, bulbar weakness, OSA, resp muscle weakness, poor cough, asp risk, scoliosis, cataracts, ptosis, cog imp, DM, low thyroid, delayed gastric emptying, weakness, wasting, balding
Blds inc CK, glu; ECG, CXR, echo, 24h tape, spirometry, flow vol loops, ABG, urine myoglobin
Sux CI, avoid all MRs if poss/10% dosing trac only
RA>LA>GA but avoid neuraxial if aut dys
TIVA (?MH link)
Resp failure commonest cause of death
Myasthenia gravis
Young women
15% have thymoma
Autoimmune
Antibodies to postsynaptic nAChR at NMJ - prevents attachment of ACh (abs detectable in 80%). If neg, 70% are positive for anti-MSK abs.
Muscle weakness that is fatiguable
Diplopia, ptosis, bulbar weakness
Myasthenic crisis - resp failure
Type 1 - ocular only
Type 2a/b - mild, responding well/not well
Type 3 - acute presentation
Type 4 - myasthenic crisis needing MV
EMG - progressive decline in amplitude
Muscle bx single fibre EMG - greater than 10% decrement on repeated compound motor action potentials.
Tensilon (edrophonium) test - test dose then bigger dose - improvement lasts 5m (worsens cholinergic crisis) - sensitive but not specific
EMG - repetitive stimulation demonstrates reduction in muscle action potential
Imaging for thymoma
TFTs to differentiate from hypothyroidism
Crisis can be triggered by cipro, Mg, BBs, gent, sux, pethidine, intercurrent illness, pregnancy, surgery
Crisis tx: high dose steroids, plasma exchange/IVIg
Anaes
Preop - CT chest to plan airway re: thymoma; spirometry, ABG, preop chest PT, ?book ICU bed
Intraop - art line, nerve stim, airway plan (AFOI/rigid bronch), resistant to sux but sensitive to NDMR (10% dosing); avoid and give remi/prop TCI
Postop - ideally extubate, PCA
Indications for postop MV: duration >6y, grade 3 or 4 MG, FVC<3L.
Tx anticholinesterases (pyridostigmine), immunosuppression.
LEMS - paraneoplastic a/w small cell ca lung, not responsive to anticholinesterases.
ARDS
Causes: pulmonary and non-pulmonary.
Stages: exudative, proliferative, fibrotic.
Berlin criteria Timing - within 1/52 of known insult Imaging - bilateral opacities not fully explained by effusions Not fully explained by cardiac failure Mild: PFR 39.9 down to 26.6kPa Moderate: 26.6 down to 13.3kPa Severe: <13.3kPa. 45% mortality. All with PEEP at least 5 cmH2O
Mx: LTVV, PEEP ladder, recruitment, conservative fluid strategy, I:E manipulation, ?APRV, paralysis
Rescue: proning, ECMO
No role: HFOV, statins, NO, beta agonists, surfactant
Controversial: steroids
Proning increases FRC, improves V/Q matching, recruits atelectatic lung, facilitates secretion drainage. Improves oxygenation in up to 80%.
Tetanus (past Q)
Clostridium tetani, anaerobic Gram negative bacteria from soil/dust/faeces (unlike botulism, which is Gram pos)
Tetanus toxin (tetanospasmin) blocks inhibitory neurotransmitter release from presynaptic and interneurones
Results in uncontrolled motor neurone activity - hypertonia, spasm and SNS disinhibition
Toxin binds irreversibly
Trismus, facial muscle spasm (risus sardonicus), truncal muscle spasm, laryngospasm, autonomic storm (tachycardia, HTN, sweating, pyrexia - alternating with bradycardia, hypotension, ultimately asystole)
Anticipate laryngospasm
Intubate early
Early trache - long wean
Spasm control - BDZ, opiates, NMDRs, sedation, baclofen
CVS instability - Mg, clonidine, atropine
?dantrolene
Tx: human tetanus Ig - intrathecal
Tetanus antitoxin SC
Metronidazole +/or ben pen
Tetanus toxoid immunisation when convalescent
Surgical wound debridement
Watch for rhabdo
Imaging
CXR: if effusion present on PA, at least 200ml. If present lateral, at least 50ml. Obscures hemidiaphragm at 500ml.
FAST can detect 200ml free fluid (operator dependent). 90% sensitive.
SVT in child (past Q)
CSM rarely works and can cause airway obstruction in babies/small children
Glove filled with crushed ice to face - diving reflex
Oculocardiac reflex not recommended (Vi - X)
Adenosine start at 100mcg/kg
Amiodarone 5mg/kg
(CSM: CI in carotid stenosis/atherosclerosis, bruit, recent TIA/stroke. Continuous monitoring, pt supine, neck extended. Carotid sinus is inferior to angle of mandible at level of thyroid, near carotid artery pulse. Apply enough pressure to indent a tennis ball for 5-10s (steady not pulsatile as more reproducible). If no response can repeat on other side after 2m.
For a patient with suspected carotid sinus hypersensitivity in whom CSM is performed, a positive response is defined as asystole for 3+ s or a >50 mmHg drop in SBP. Diagnostic rate increases when performed upright.)
Guillain-Barre syndrome
Autoimmune - believed to be result of abs produced against pathogens cross-reacting with neuronal myelin sheaths. Result = demyelination of peripheral nerves.
Symmetrical ascending weakness, areflexia, cranial nerve palsies, back pain, peripheral parasthesiae and other sensory deficits. Autonomic involvement: orthostatic hypotension, dysrhythmias, sweating, urinary retention, gut dysmotility.
Differentials: MG, LEMS, MND, CNS infection (men/enc/transverse myelitis), MS/NMO, botulism, critical illness weakness.
Associations: Campylobacter (40%), CMV (15%), Mycoplasma (5%), EBV, HIV, SLE, lymphoma, sarcoid.
Clinical diagnosis. Ix: SIADH, deranged LFTs, anti-GM1 abs (poor prognosis), CK, ESR. High protein on CSF. ECG abnormalities. Nerve conduction studies - slowing of motor conduction velocity. HIV. Stool cx for Campylobacter. Viral screen.
20/30/40 rule for critical care admission
VC <15-20ml/kg
Max insp pressure worse than -30cmH2O
Max exp pressure <40 cmH2O
Tx: supportive, IVIG (0.4mg/kg for 5d, start within 2/52; SEs nausea, headache, fever, deranged LFTs, erythroderma, renal tubular necrosis, anaphylaxis), plasma exchange (250ml/kg plasma replaced with 4.5% HAS, 3-5 treatments of 40-50ml/kg over 5-8 days - can cause hypotension, hypocalcaemia, coagulopathy), CSF filtration. Steroids no benefit and may cause harm.
CI to IVIG = IgA deficiency (higher risk of anaphylaxis), previous anaphylaxis; relative = renal impairment, CCF.
25-30% need MV (VC<20 needs critical care, VC<15ml/kg/MIP30% needs I+V). NIV not useful as does not address inability to manage secretions. Avoid sux and anticipate CVS instability on induction. Early trache - long wean. MDT.
Comps: resp failure, autonomic neuropathy, persisting neurological deficit (10%), mortality 5%.
Alcohol abuse
GI: pancreatitis, hepatic steatosis, alcoholic hepatitis, cirrhosis, hepatocellular ca, gastric/oesophageal/colonic ca, portal HTN, varices, delayed gastric emptying, ascites
CVS: DCM, arrhythmias, conduction defects
RS: high concordance with smoking
Metabolic/endo/nutrition: malnutrition, hypoglycaemia, electrolyte disturbance, low albumin, reduced adrenocortical stress response
Haem: low plts, macrocytic anaemia, coagulopathy
CNS: Wernicke, Korsakoff, depression, withdrawal/DTs
Immune: immunosuppression, high risk postop infection
Anaphylaxis
Allergic anaphylaxis has an incidence between 1/5000–1/20 000 with a 3:1 female preponderance.
Skin prick testing only elicits IgE-mediated allergy. Negative tryptase also does not exclude serious allergy. Tryptase is measured in preference to histamine as the half life of the latter is too short.
Tests: skin prick, intradermal, RAST (now superseded by CAP), drug challenge.
Triggers: MRs 60% (sux most common; lots of cross-reactivity; 80% occur without prior sensitisation), latex 15%, abx, colloids, chlorhexidine.
Topical agents will take longer to manifest a reaction. Tourniquet may also delay onset.
In 40%, the suspected allergen turns out to be incorrect.
Environmental exposure is more important than genetics. Therefore family screening not indicated.
Polycythaemia
Primary: polycythaemia rubra vera
Secondary: chronic lung disease, high altitude, cyanotic CHD, OSA
Haemoconcentration is seen in dehydration and burns which can mimic polycythaemia.
Increased risk of VTE and stroke.
Carcinoid syndrome
Systemic manifestation of carcinoid tumour.
From argentaffin cells –> production of peptides and amides, which are metab by liver so no sx until tumour metastatic (or if non-GI)
75% in GIT, usually terminal ileum (others bronchus, pancreas, gonads)
Usually benign
5HT, kinins, PGs, histamine and substance P
Sx due to tumour: haemoptysis, intenstinal obstruction
Sx due to peptides: diarrhoea, flushing, wheeze, tachycardia, BP up or down, hyperglycaemia, RHF secondary to endocardial fibrosis
Diagnosis: measure 5HIAA (serotonin metabolite) in urine
Tx: octreotide (somatostatin analogue) - reduces vasoactive peptide production/release; reduces splanchnic flow. Also used in acromegaly, VIPomas and varices.
Anaes
Preop: bronchodilators, rehydration, correct electrolytes, octreotide for 2/52, BDZ premed, avoid triggering a carcinoid crisis (catecholamines, histamine-releasing drugs)
Intraop: invasive lines, fully obtund pressor response, avoid sux as increased IAP could increase mediator release, avoid morphine/trac, treat hypotension with octreotide first line (beta blockers second line; avoid catecholamines)
Postop: crit care, more octreotide
5HT (i.e. serotonin) is broken down by MAOi into 5HIAA and melatonin
Effects of 5HT
- Diarrhoea, vomiting
- Water and electrolyte secretion/loss
- Inhibitory neurotransmitter
- Increases plt aggregation
- Bronchoconstriction
Needlestick
Usual stuff
Consider passive immunisation - HBV Ig/booster, antivirals, abx, anti-tetanus
Risk assessment: wound, donor and recipient factors
PEP - two nucleoside reverse transcriptase inhibitors (lamivudine) and one protease inhibitor (ritonavir)
Universal precautions
- Hand washing
- Gloves
- Gown/apron/eye protection
- Sharps management
COPD
Obstructive airways disease which does not display reversibility. Overwhelmingly (>95%) caused by damage from smoking. Spectrum from emphysema (destructive enlargement of airspaces by bullae) and chronic bronchitis (clinical diagnosis of productive cough >3/12 of year for >2 consecutive y)
Emphysema occurs because of hyper-production of elastase which breaks down elastin. Alpha 1 antitrypsin is the natural inhibitor of this enzyme. In smoking, elastase activity outweighs that of A1AT. Hence A1AT is other cause of COPD. Emphysema typically affects lower lung fields, A1ATd upper.
Ipratropium: non-selective competitive mAChR antagonist
Problems periop
- Bronchospasm/laryngospasm
- Sputum plugging
- V/Q mismatch
- PTX
- RHF from HPV
LTOT indications - PaO2<7.3 or <8.0 with complications (polycythaemia/PHTN).
Sepsis
Inflammatory cascade of cytokines and adhesion molecules
Complement and coagulation pathways activated
Nitric oxide released in large quantities - vasodilatation
Enhanced recovery
Preop: ax, optimisation, correction of anaemia, booking of postop ICU bed, education, admit on the day, minimise fasting, carb load, no bowel prep, paracet/NSAID load
Intra-op: min invasive surgery, RA, neuraxial for abdo, avoid NG/drains, GDT/CO monitoring, normothermia, short-acting anaesthetic agents
Postop: early nutrition and mobilisation, multimodal analgesia, aggressive rx PONV, MDT follow up post discharge
Reduces avoidable postop comps e.g. ileus, LRTI, VTE.
Colorectal, urology, ortho, gynae
LA toxicity (RCoA new book)
Mechanism - blocks Na channels from within cells RFs - Operator - dose, speed of injection- Site - vascularity - Pharmacological - potency, PPB, clearance Effects - CVS/CNS Management - Intralipid 20% 1.5ml/kg over 1m, 1.5ml/kg/hr; max 3 boluses/double rate
Antihypertensives (RCoA old book, Krishnachetty)
By site of action: Heart: ABs, BBsBlood vessels: direct (GTN, SNP) and indirect (CCBs), K+ channel activators (nicorandil) Kidney: ACEi, ARB, diuretics, direct renin inhibitors CNS: methyldopa, clonidine, dexmedetomidine, ganglion blockers e.g. trimetaphan Or by part of equation: MAP = (HR x SV) x SVR Or by mechanism: - Drugs that act on RAAS and mainly reduce SVR - Drugs that increase Na+ and H2O excretion and mainly reduce preload Causes: primary (essential), secondary (renal, endocrine, vascular). New agents: direct renin inhibitors (aliskiren). No bradykinin accumulation. <3% bioav. Only for resistant HTN. May cause severe hypotension intraop. Causes diarrhoea. Age <55: ACEi. Age >55 or black: CCB. SNP: 0.3-0.5mcg/kg/min. Protect from light - cyanide (antidote hydroxycobalamin).
Flumazenil (RCoA old book, Mendonca)
Competitive BDZ receptor antagonist for iatrogenic BDZ overdose Rapid distribution, peak effect in 5m, duration <1h Metabolised by liver Can increase ICP and lower seizure threshold; N&V, flushing, anaphylaxis Dose up to 600mcg over 5m, max 1mg; infusion 100-400mcg/h
MAOi (RCoA old book, past Q)
Enzyme present in liver and nervous system; isoenzymes A and B Part of the inactivation mechanism for naturally occurring vasoactive substancesMAOi: irreversible A and B inhibitors e.g. phenelzine (the problematic type); reversible MAO-A e.g. moclobemide, reversible MAO-B e.g. selegiline. Reduce breakdown of catecholamines SEs: sedation, orthostatic hypotension, liver toxicity Interaction with opioids - problems with postop analgesia - Type 1 (excitatory): pethidine –> serotonin syndrome - Type 2 (depressive): enhanced respiratory depression, due to hepatic enzyme inhibition Indirectly acting vasopressors can cause fatal hypertensive crisis - phenylephrine safe; careful titration of direct agents Pancuronium can release stored NA TCAs can cause hyperpyrexia and cerebral irritation Withdraw at least 2/52 preop (new enzyme has to be formed). Can continue selegiline <10mg/day, just avoid pethidine D/w psych/MDT, withdrawal risk/benefit, risk of discontinuation syndrome and relapse If can’t stop, BDZ premed, hydration, cautious titration of phenyl, RA if able (avoid adrenaline), indirect sympathomimetics/pethidine abs CI Cheese (tyramine) reaction with cheese, yeast, alcohol, chocolate, cream, broad beans
Drugs acting on the uterus (RCoA old book, past Q)
Uterotonics
- PGs (E2, F2a) - abortion, IOL. Latter can cause bronchoconstriction (carboprost)
- Oxytocin - initiation/maintenance of labour, PPH control
- Ergometrine - alpha 1 and 5HT agonist. Can cause severe HTN, vomiting and bronchospasm
Tocolytics
- Beta 2 agonists - salbutamol, terbutaline, ritodrine
- CCBs - nifedipine - headache, nausea
- MgSO4 - competitive calcium antagonist and NM blocker, vasodilator and anticonvulsant
- Volatiles - dose related uterine relaxation
- GTN - NO donor - used in retained placenta, uterine inversion
No effect: IV anaesthetics, analgesics, NDMRs, reversal agents
Drugs used in cancer (Krishnachetty, Dr Barry)
Disease-modifying vs symptom control
Cytotoxics - plantinum-based, antimetabolites, alkaloids, topoisomerase inhibitors, antitumour antibiotics, steroids, monoclonal antibodies. (Sx - analgesics, antiemetics, anxiolytics, antisialogogues.)
SEs: bleomycin - pul fibrosis and O2 toxicity, doxorubicin - cardiotoxic, platinum agents - nephrotoxic, methotrexate - hepatotoxic and neurotoxic, most agents - myelosuppression, neutropenic sepsis, nausea and vomiting, anorexia, alopecia. Tumour lysis syn: high K/PO4 (precipitates in kidneys)/uric acid, low Ca. Prevent with hydration, alkalinisation of urine, allopurinol, rasburicase. Things to avoid in cancer: N2O (?accelerates metastasis), ?volatiles
Antibiotics (past Q, Dr Barry)
Inhibit synthesis one of three bacterial components:
- cell wall - beta lactams
- protein (30s/50s) - aminoglycosides, macrolides
- DNA - fluoroquinolones
Classification
- Bacteriocidal - kill orgs
Beta lactams, aminoglycosides, cephalosporins, vanc, cipro, metro
- Bacteriostatic - prevent growth
Macrolides, clinda, trimethoprim, tetracycline
- Concentration dependent e.g. aminoglycosides
- Time dependent (time above MIC) e.g. beta lactams
Resistance
natural e.g. thick cell wall of Gram -ves
vertical gene transfer - spontaneous mutations
horizontal gene transfer e.g. transduction
When are abx not required? Routine OGD/colonoscopy, dental, genitourinaryHigh risk of endocarditis: valvular disease, valvular replacement, HCM, previous IE, CHD (excluding lone ASD or repaired VSD/PDA).
Reasons for non-resolving infection
- resistant organism
- wrong abx
- immunodeficiency
- abx not penetrating e.g. abscess needing drainage
Calcium channel blockers (Mendonca)
Ind: HTN, angina, PHTN, arrhythmias, vasospasm prophylaxis in SAH, migraine, Raynaud’s. Types of Ca channel: L, T, N, P. CCBs block L-type channels. Reduces Ca level in cells, thereby reducing muscle contraction. In heart, reduces HR and contractility. In vessels, relaxes smooth muscle –> vasodilatation. Unlike BBs, CCBs do not reduce the responsiveness of the heart to sympathetic input. Dihydropyridines: amlod, nifed. Reduce SVR and BP. Non-DHPs: verapamil (phenylalkylamine) - more cardioselective. Diltiazem (benzothiapine) - middling class. PD: vasodilatation, negative inotrope/chronotrope/dromotrope. Can cause heart block/heart failure. Also flushing, HA, palps, pedal oedema. HTN <55: ACEi. >55/black: CCB. Interactions: BBs - heart failure/block/severe hypotension. Diuretics - severe hypotension. Digoxin levels may rise. Dihydropyridines (amlodipine) - reduce SVR Phenylalkylamine (verapamil) - cardioselective Benzothiazepine (diltiazem) - middling class
PCA (Mendonca)
Pros: superior analgesia, pt satisfaction, avoids IM injections, reduced nursing workload. Principle of ‘autoregulation’/negative feedback (no demands if drowsy). Minimum effective analgesic concentration is individual to pt. PCA pump: computerised, programmable, battery-operated portable pump. Microprocessor stores data. Button and timer. Safety features: lockout time, max hourly dose, alarms, anti-siphon, keep pump at pt level, lockable cage. Obs and sedation score monitoring. Rx O2, naloxone, prescription, contact available for advice. Types of PCA: IV, SC, epidural, peripheral nerve catheter, transdermal.
Neuromuscular blocking drugs (Mendonca, past Q)
Sux - see separate card. Depolarising agents (sux, decamethonium) - faster onset, fasciculation, reduced single twitch and TOF equal reduced height, no fade, no post-tetanic facilitation. Non-competitive - cannot be overcome. Non-depolarising - slower onset, no fasciculation, reduced single twitch and reducing height in TOF, fade and post-tetanic facilitation. Competitive - can be overcome. Benzylisoquinolinium esters - trac, cistrac, miv; broken down by non-specific esterases and Hoffman degeneration Aminosteroids - vec, roc; mainly hepatic excretion, and 40% renal. Prolongation of NDMRs: hypokalaemia, hypocalcaemia, hypernatraemia, hypermagnesaemia, acidosis, liver/renal failure, hypothermia, aminoglycosides, LAs, volatiles, CCBs, anticholinesterases, lithium. Reversal Neostigmine 10mcg/kg - an anticholinesterase. Prevents ACh being broken down and also increases ACh release. XS dosing can cause depolarising type block. SEs: bradycardia (muscarinic effect), hypotension, hypotonia, bronchospasm/constriction, salivation, peristalsis; hence glyco given (similar onset time). Onset 1m, peak 10m, metab by plasma esterases. Sugammadex: modified gamma cyclodextrin. “Su” = sugar, “gammadex” = structural molecule, gammadextrin. Forms tight 1:1 complexes with aminosteroid MRs. This then creates a conc gradt away from NMJ into plasma. 2/4/16mg/kg for moderate/deep block/immediate reversal.
NSAIDs (Mendonca)
Non-specific vs COX-2 specific e.g. celecoxib (also preferential COX-2 e.g. meloxicam). COX-1 constitutive, COX-2 inducible (latter only formed when tissues exposed to inflammatory stimuli; made by macrophages). Inhibition of COX-1 causes SEs and anti-plt function. Inhibition of COX-2 gives analgesia and anti-inflammatory (hence was the target in COX-2i development). COX-2s have reduced GI SEs but increased stroke and MI (VIGOR trial - rofecoxib vs. naproxen). Mechanism = affects PC:TXA2 ratio so latter more abundant, promoting atherosclerosis and thrombosis. Also Na+/H2O retention causing HTN. SIde effects of NSAIDs- Increased gastric acid secretion and reduced gastric blood flow - dyspepsia, N&V, GI bleed - 10-20% asthmatics are sensitive to leukotrienes - Renal impairment (reduced RBF/GFR) - Bleeding (plt dysfunction) - even more so with warfarin (displaced) Arachidonic acid pathway Paracetamol - sometimes classed as NSAID as may inhibit COX. May also modulate endogenous cannbinoid system. Metabolised mainly to sulphate and glucuronide conjugates, and also to NAPQI by P450 system (normally conjugated with glutathione and renally excreted). In OD, more is shunted down NAPQI pathway and glutathione is depleted. NAPQI causes hepatocellular damage (zone 1). NAC replenishes glutathione.
Remifentanil (Mendonca, past Q)
Synthetic pure mu agonist. Used as adjunct for induction and maintenance (TIVA) of anaesthesia, hypotensive anaesthesia, analgesia e.g. in labour, and ICU sedation. Ultra short-acting. 1, 2 or 5mg hydrochloride salt in glass vial to be made up as solution. 0.05-0.2mcg/kg/min/TCI 3-8ng/ml (8-10ng/ml for intubation without MR). Hydrolysed rapidly by red cell and tissue esterases to caboxylic acid. Pros: controlled ventilation without NMBs so can nerve monitor, titratable hypotension, stable HR, excellent analgesia, prevents coughing - smooth emergence, context insensitive, reduced PONV, predictable recovery, does not require dose adjustment in hepatic/renal disease, reduces MAC of volatiles Cons: no postop analgesia, risk of awareness if TIVA (and need dedicated line), remi-induced hyperalgesia, chest wall rigidity, cannot be used as sole agent, bradycardia pKa 7.1, 80% ionised Remi PCA in labour:Unlicensed indication. Not if pethidine within last 4h. Dedicated cannula, nasal O2, naloxone prescribed, BVM in room, midwife 1:1, SpO2 monitoring. 10% incidence of desaturation. RS: resp depression, apnoea, chest wall rigidity, reduced response to hypoxia/hypercapnoeaCVS: reduces HR, BP, COCNS: reduces CBF and ICP, preserves autoregulationElderly: increased sensitivity, reduced VD and clearance - therefore bolus and rate need 50% reduction. Uses: induction/airway control/AFOI, middle ear, neuro, cardiac, ICU, bariatrics.
Alpha-adrenergic blockers (Mendonca)
Non-selective - phenoxybenzamine (long acting, PO preop for phaeo), phenotolamine (short acting, IV intraop for phaeo). Cause vasodilation/reduced SVR, and reflex tachycardia. Phentolamine contains sulphites in the ampoule which can cause bronchospasm in asthmatics. Selective (alpha-1) - doxazocin, prazocin Selective (alpha-2) - yohimbine
Post-herpetic neuralgia (Mendonca, past Q)
Varicella zoster. Virus stays dormant for decades in sensory root ganglia. Age >50 Hyperasthesia, parasthesia, burning pain, pruritis prodrome. Then rash - vesicles take 10/7 to crust over. T5/6 or ophthalmic with eye comps. TxGeneral: cool bath, loose clothes Topical: capsaicin (exhausts supplies of substance P), LA patches Pharm: paracetamol, NSAIDs, gabapentin, pregabalin, amitriptyline (TCAs are slower to work and have anticholinergic SEs), antivirals within 72h Interventional: LA infiltration, sympathetic blockade, nerve blocks, epidural steroids Other: TENS, behavioural Gabapentin: NNT 4 (for pain reduction >50%). Has affinity for alpha-2-delta subunit of presynaptic Ca2+ channels. On binding it prevents Ca2+ influx and release of neurotransmitters. Gabapentin may reduce or reverse opioid tolerance and is synergistic with morphine.
Oral hypoglycaemic drugs (Mendonca, past Q)
Increase insulin sensitivity
- Biguanides (metformin)
- Thiazolidinediones (pioglitazone)
Increase insulin secretion
- Sulphonylureas (gliclazide)
- Dipeptidyl peptidase IV inhibitors (sitagliptin)
- Meglitinides (repaglinide)
- Incretin mimetics (exenatide)
Other
- Alpha glucosidase inhibitors (acarbose) - reduce carbohydrate absorption
Drugs for Parkinson’s disease (Krishnachetty, past Q)
Phenylalanine –> L-tyrosine –(tyrosine hydroxylase - rate-limiting step)–> L-dopa –> dopamine –> NA –> A PD: 1% of >65s Drugs:- Dopamine precursors e.g. levodopa (with dopa decarboxylase inhibitor e.g. benserazide) - Dopamine agonists e.g. apomorphine - MAO-B inhibitors e.g. selegiline - COMT inhibitors e.g. entacapone - Anticholinergics e.g. orphenadrine- Atypicals e.g. amantidine Periop: avoid missed doses, can use SC apomorphineAvoid: atropine (central anticholinergic syn), pethidine, metoclopramide, droperidol, prochlorperazine, classical antipsychotics (all worsen sx)Caution with antihypertensives (can cause severe hypotension), TCAs (arrhythmias)Do give: domperidone, glycopyrrolate
Serotonin (Krishnachetty)
Serotonin = 5HT. Made from tryptophan (essential AA). Found in plts, GIT, CNS. Receptors 5HT-1 to 7 exist - most GPCR and act via adenyl cyclase. Serotonin syndrome - serotonin excess in CNS. Triad: altered mental status, autonomic dysfunction, neuromuscular excitability. Can lead to rhabdo, DIC, AKI. Hunter criteria: pt has taken serotonergic agent (SSRI, TCA, MAOi, pethidine, ondansetron, fentanyl, tramadol, alcohol, cocaine, ecstasy, LSD) and has one or more of: clonus, agitation, diaphoresis, tremor, hyperreflexia, hypertonia, pyrexia. Diagnosis is clinical. Underdiagnosed. May see raised WBC/CK. Tx withdraw agent, supportive. Cyproheptadine is serotonin antagonist.
Tricyclic antidepressants (Krishnachetty, past Q)
OD: CVS (palps, CP, tachy, hypotension, ECG changes, CNS (agitation, visual dist, hyperreflexia, clonus, seizures), anticholinergic (dry mouth/skin, urinary retention) Mechanisms: anticholinergic, H1/2 antagonism, blockade of presynaptic reuptake of catechols, alpha 1 antagonism, blockade of cardiac fast Na+ and delayed K+ channels (slow phase 0) Peak levels 2-4h post PO, large Vd, high PPB, liver metab, active metabs. Rx: charcoal, bicarb (reduces free fraction), BDZ for seizures, treat arrhythmias, ECG monitoring, alkalinise urine. Glucagon?
Drugs used for secondary prevention (Krishnachetty)
To reduce risk of further MI. ACEi, BB, antiplts, statins. ACEi - post MI, HTN (<55 and not Afro-Caribbean), CCF, diabetic nephropathy, CKD. SEs dry cough, refractory hypotension with GA, angio-oedema (more common in Afro-Caribbeans). Clopidogrel: ADP receptor blocker Aspirin: COXi DES: sirolimus (TORi), paclitaxel (alkaloid)
TIVA/TCI (Krishnachetty, past Q)
TIVA ind: when volatiles unavailable, undesirable, or CI. TIVA desirable drug features: low Vd, rapid metabolism, short CSHL or context insensitive. PC/PK/PD properties of ideal agent. Components: user interface, microprocessor and infusion device. 3 compartment model: central, vessel-rich and vessel-poor. CSHT is a comparison between the distribution and elimination clearances. Low Vd and high elimination desirable. After 2h and 4h, ratio of distribution clearance to elimination clearance for fentanyl is 5:1 (48m –> 250m), propofol 1:1 (16m –> 20m), remi <1 (4.5 –> 6m). Remi model = Minto (weight >30kg, age>12), Davis/Rigby-Jones (not widely available) Paeds propofol = Paedfusor >5kg, Kataria >15kgTypical plasma conc: remi 3-8ng/ml (up to 10-15 during stimulating procedures), propofol 5-8mcg/ml TCI pumps recalculate effect site conc at 10s intervals and either bolus or stop when different desired concs are entered. Rate of equilibration between blood and effect site depends on rate of drug delivery, cardiac output, cerebral blood flow, lipid solubility and degree of ionisation of drug. Models for propofol * Marsh: assumes central compartment volume is directly proportional to weight. Age is entered but not utilised (although pump will not work if age <16 entered). Risk of overdosing obese pts, therefore use ideal body weight rather than total. * Schnider: newer, 3-compartment. Age, height, weight entered. Lean body mass calculated and used. Central compartment assumed to be same for every pt. Uses less propofol overall. Better for elderly as takes age into account (lower Cl). Schnider central compartment (4.27L) is a quarter of the size of that of Marsh (15.9L).for a 70kg pt. In combined propofol/remi, start propofol first as effect site conc slower to rise (also pt may stop breathing before LOC with remi). Cons of TCI: all TIVA concerns (awareness etc), no postop analgesia, no definitive monitor analogous to EtAA (use BIS; models with BIS feedback under development), models are from healthy volunteers only. How can you do TIVA without a TCI pump? - Loading: desired conc x VD - Maintenance: desired conc x clearance Which compartment closest resembles brain? Why does TCI value not match blood sample level? Would children be over or underdosed on an adult TCI model?
Anticoagulants and bridging (Krishnachetty, past Q)
Antiplatelets: asp, clop (ADP receptor blocker), dipyridamole (PDEi), glycoprotein 2b/3as Heparins: UFH, LMWH, Xa inhibitors (fonda) VKAsNOACs- DTIs - dabigatran - Xa i - rivaroxiban Reversal of warfarin- Vitamin K - PO/IV works in 4-6h (up to 5mg), 2-4h (5-10mg) - PCC 50mg/kg (irradiated pooled human plasma) - 30m, lasts 6-12h. Contains CFs 2/7/9/10, + protein C and S and sometimes heparin (to combat prothrombotic tendency) - FFP (all clotting factors + fibrinogen) - no longer recommended - partial effect, fluid overload - Stop warfarin - 2-4 days Warfarin - synthetic coumarin derivative, VKA (2/7/9/10). Heparin - activates antithrombin 3 (inhibits CFs 2/9/10/11/12). Fractionated = average MW <8kDa. Unfractionated = 3-30kDa. LMWH pros: less frequent dosing, SC, no monitoring, lower risk of HIT Heparin pros: quick on/offset - better control and monitoring, can reverse with protamine Other drugs- Fondaparinux - synthetic analogue of part of heparin - Xa inhibitor - rivaroxaban (RECORD study - fewer VTEs in LL arthroplasty and comparable bleeding rates to warfarin) - Direct thrombin inhibitor - dabigatran LSCS - 10/7 LMWH standard, 6/52 if high risk 1 unit of activity = the amount required to keep 1ml cat’s blood liquid for 24h at 0C.
Suxamethonium (past Q)
Sux = two ACh molecules bound together. Competes with ACh for post-synaptic nAChR binding sites. Binds to alpha subunit (of the pentameric nAChR). Keeps ion channel open longer than ACh would. Ca2+ and Na+ go in, K+ goes out. SEs: hyperkalaemia (increases K+ by 0.5mmol/L. Avoid if K+>5.5), myalgia (young muscular ambulatory pts), bradycardia (children, repeated dosing), sux apnoea (cholinesterase deficiency), transient increased IOP/ICP and intragastric pressure (but oesophageal sphincter pressure also rises so no increased risk of regurg), MH trigger, tachyphylaxis and phase 2 block (akin to non-depolarising block), histamine release, anaphylaxis. Bradycardia is caused by the initial metabolite of sux, succinylmonocholine, which stimulates mAChRs in the heart. Sux apnoea Plasma cholinesterase deficiency Eu = normal (94% pop EuEu) Ea (atypical i.e. dibucaine-resistant), Es (silent), Ef (fluoride-resistant) Dibucaine testing (dibucaine is a LA that inhibits normal plasma cholinesterase by 80%): - Normal dibucaine number = 80 (94%) - EaEu 60 (4%)- Others rare, number down to 30 Mivacurium is subject to same breakdown pathway. Options: sedate until wears off; FFP Acquired sux apnoea: preg, liver/renal/cardiac disease
Opioids (past Q)
Opioids are weak bases - highly ionised in acidic stomach so poorly absorbed, better absorbed from small intestine. High 1st pass metab. High lipid sol and high VDs. Liver metab, excretion in urine/bile. Classifications: strong/intermediate/weak, naturally occuring/synthetic/semi-synthetic, pure/partial/mixed agonists/antagonists. Pure agonists - morph/fent/remi/ Partial agonist - buprenorphine, tramadol Mixed agonist/antagonist - nalbuphine Antagonists - naloxone - duration 30m; infusion 5-10mcg/kg/h. Naltrexone - longer half life, works for 24h. Used in addiction and compulsive eating. Oral equivalence ratios: Morphine 1 Oxycodone 2 Tramadol 0.15 Codeine 0.1 Transdermal: Buprenorphine 5mcg/h patch = 12mg Oramorph over 24h Fentanyl 50mcg/h patch = 180mg Oramorph over 24h Many of the SEs of opioids result from peripheral receptor agonism (whereas desirable effects are central) - methylnaltrexone (peripheral antagonist) reduces these. Receptors - all GPCRs All reduce neuronal cell excitability and nerve impulse transmission, and inhibit neurotransmitter release. Activation of opioid receptors causes closing of calcium channels, K+ efflux and hyperpolarisation. - MOP - throughout CNS; produces resp depression by making chemoreceptors less sensitive to CO2, constipation, meiosis, itch.- DOP - cerebral cortex; less widespread; resp depression, GI SEs. - KOP - nucleus raphe magnus; sedation, dysphoria. NO resp depression. Meiosis. - NOP (non-classical) - role in synaptic plasticity - basis of tolerance and dependence. Does not bind to naloxone. Can be anti-analgesic. Morphine - peak 30-60m, terminal half life 3.5h. Metab by gut and liver to 70% M3G and 10% M6G (13x more potent). Fentanyl - metab to norfentanyl (inactive). Peak 3-5m, duration 30m. Terminal half life 3.5h. Pethidine - metab to norpethidine (active - hallucinations, seizures). Codeine - CYP2D6. Poor and fast metabolisers.
ACE inhibitors (past Q)
Prodrugs: enalapril, ramipril, perindopril (–> enalaprilat etc). Given as prodrugs because improves gut absorption. Active drugs: lisinopril, captopril Ind: HTN <55y, heart failure, post MI, diabetic nephropathy, CKD. SEs: dry cough (bradykinin), first dose hypotension, refractory hypotension under GA (avoid AM dose), renal impairment, angio-oedema, teratogenicity. Other prodrugs: codeine, cyclophosphamide, isoniazid, clopidogrel, levodopa. A prodrug is a compound that has little or no activity on a desired pharmacological target, but is converted to an active, or more active, entity by an endogenous metabolic reaction. Prodrugs can improve pharmacokinetics, reduce toxicity, or facilitate delivery of the drug to specific tissues or cells.
Magnesium
2nd most abundant intracellular cation25g in adult body, mainly in bone Antihypertensive - Calcium antagonism (prevents Ca entry to cells via NMDA channels) - reduces vasospasm - Direct vasodilator - Decreases catecholamine release from adrenals Anti-arrhythmic - Reduces SAN/AVN conductionSmooth muscle relaxant - Reduces presynaptic ACh release - Reduces sensitivity of postsynaptic membrane Other roles- Enzyme cofactor - Anticonvulsant Therapeutic 2-4 mmol/L Loss of reflexes >5Respiratory depression 6-7 Cardiac arrest >10-12
Thiopentone (past Q)
How did NAP 5 suggest that thio contributes to awareness? Always used with NMB, in RSIs/emergencies N2 in vial as CO2 in air would react –> precipitates Intra-arterial injection Precipitation of acid crystals –> occlusion and spasm of vessel –> critical ischaemia Stop injecting, keep line in, run in 500ml warm saline, 10ml 1% lidocaine if severe pain, vasodilators e.g. papaverine; then stellate ganglion block or BP block to induce sympathetic blockade, then fully anticoagulate (500-1000u heparin). Vascular opinion. IR1, document, consultant.
Anaphylaxis (past Q)
Incidence of each sign/symptom Specific drug precipitants Anaphylactic vs anaphylactoid Latex is slower reaction as transdermal rather than IV insult Sugammadex for vec/roc anaphylaxis
Tranexamic acid
Synthetic lysine derivative
Antifibrinolytic
Prevents conversion of plasminogen to plasmin
CRASH-2
WOMAN April 2017 - reduces death from PPH by 19%
Local anaesthetics (past Q)
Isomers Esters and amidesToxicity - which pts at risk? R-bup - cardiotoxic as binds to myocytes and affects mem potential What preservatives used?
Drugs for TBI (past Q)
Intubation and ongoing sedation in ICU Management of complications including seizures and raised ICP Sevo is used over des because causes lesser increase in CBF.
Beta blockers (past Q)
Cardioselective: metoprolol, atenolol, esmolol Non-cardioselective: propranolol, sotalol Most are pure antagonists but some are mixed agonist/antagonist (e.g. timolol) Non-cardiac indications: propranolol for migraine prophylaxis; varices; thyrotoxicosis; anxiety POISE trial - newly started beta blockers reduce perioperative MI but increase stroke. Therefore leave pts on them but do not newly start them. Esmolol: 10mg bolus, or 50-200mcg/kg/min. Labetalol: 5-20mg bolus, up to 200mg.
Propofol
2,6-diisopropylphenol - a sterically hindered phenol GABA-A agonist Induction and maintenance of GA, sedation Emulsion contains soya bean oil, egg phosphatide and glycerol Isotonic to plasma pH 7.0-8.5, pKa 11 (almost entirely unionised at physiological pH) VD 4L/kg Induction 1-2.5mg/kg, titrated to response (loss of verbal contact)Maintenance 4-8mcg/ml 98% PPB Redistribution 2m, terminal elim half life 5-12h Vasodilator - ?NO release; HR will rise reflexively unless also given opiates Coughing/laryngospasm rare - good for LMAs Excitatory in 10% Metab in liver: 40% glucuronide, 60% quinol Clearance is greater than hepatic flow so must be some extra-hepatic metab Problems: PRIS, mortality in paeds sedation, green hair/urine
Routes of drug delivery (past Q)
Bioavailability, pharmacokinetics, intrathecal delivery systems 1st pass metabolism 1st and zero order kinetics - drug examples Intrathecal delivery systems Other sites of first pass metabolism: lungs and gut
Drugs for asthma (past Q, Mendonca)
Salbutamol: beta 2 agonist. Racemic. Stimulates GPCR –> activates adenyl cyclase to convert ATP into cAMP –> activates protein kinase A –> catalyses phosphorylation of intracellular proteins involved in control of smooth muscle tone. Also increases intracellular Ca by inhibiting its release. At low dose, beta 1 effects predominate; at high dose beta 2 (+ve inotrope, chronotrope, HTN, arrhythmia). Also tremor, agitation, hypokalaemia. Factors determining effect: route; if inh, particle size, velocity, airway size, inhaler technique. Theophylline: methylxanthine derivative. Phosphodiesterase inhibitor, adenosine antagonist, reduces Ca influx into smooth muscle cells. Phosphodiesterase is the enzyme that breaks down cAMP, so inhibiting it increases cAMP. 200-600mg TDS. Aminophylline is converted to theophylline. Loading dose 5mg/kg over 30m, then 0.5mg/kg/h. Narrow therapeutic range 10-20mg/L. SEs tachycardia, agitation, seizures, hypokalaemia. Metabolised by liver. Steroids: anti-inflammatory so reduce mucosal swelling. Reduce cytokine production. Improve bronchial hyperactivity. Montelukast: leukotriene antagonist. Prevents leukotriene binding to its receptor. 10mg OD. Can cause eosinophilia. Doxapram: acts on peripheral chemoreceptors to increase MV. 0.5-1mg/kg. SEs: increased catecholamine release, hallucinations, seizures. CI in IHD.
Anti-arrhythmics
Vaughan-Williams I-IVPhases prolonged = “0, 0+4, 3 and 0”
Anticonvulsants
GABA enhancers- BDZ - Barbituates - Valproate- Vigabatrin (prevents GABA breakdown)
Na flux modulators (reduce Na+ influx, stabilising cell mems) - Phenytoin - Carbamazepine
Ca channel blockers
Diuretics
By site of action in nephron
CAi - reduce the H+ generated for excretion
Thiazides - inhibit Na resorption at DCT
Loops - inhibit Na resorption at LoH
Osmotic - cause osmotic diuresis
K-sparing - block Na/K exchange
Prokinetics
By receptor: D2, AChE (neostigmine), 5HT4, erythromycin
Antiemetics
By receptor: H1, D2, 5HT3, mAChR, steroid
Novel - aprepitant - substance P/neurokinin antagonist
Non-pharm - acupressure of P6
Vasoactive drugs
Inotropes
- beta agonists (adrenaline, ephedrine, dobutamine, dopamine, dopexamine)
- PDEi (milrinone)
- Ca2+ sensitisers (levosimendan, glucagon)
- other (digoxin, Ca, thyroxine)
Vasopressors
- vasopressin
- metaraminol
- NA
- phenylephrine
IV fluids
Crystalloids: hypotonic, isotonic and hypertonic
Colloids: natural (albumin) and synthetic (gelatins, starches)
CNS stimulants
Psychomimetic (ketamine)
Psychomotor (cocaine, amphetamines)
Respiratory (doxapram) Amphetamines: ADHD, narcolepsy. Deplete NA. Caution++, stop preop.
Anticholinergics
Antimuscarinics (atropine, glyco, ipratropium, tropicamide)
Antinicotinics (muscle relaxants, ganglionic blockers and centrally acting) SEs: lack of fluid everywhere
Anticholinesterases (cholinesterase inhibitors) (past Q, Krishnachetty)
aka “procholinergics”
Prevent breakdown of ACh by inhibiting AChE (occupy its active site).
SEs: DUMBBELS
Ind: reversing NDMRs, Tensilon test for MG, tx for paralytic ileus, glaucoma; active ingredient in pesticides (TEPP) and nerve gas (sarin)
Classification
- Prosthetic e.g. edrophonium
- Acid-transferring e.g. pyridostigmine, neostigmine, rivastigmine, donepezil (and also the organophosphates e.g. sarin, VX)
Classification: short, medium and long acting. Or: - reversible easily e.g. edrophonium (amine) (improves MG, worsens cholinergic crisis) - binds to AChE competitively - reversible slowly - formation of carbamylated enzyme complex e.g. neostigmine, pyridostigmine (esters) - complex is hydrolysed slowly- irreversible e.g. organophosphates - form a stable complex and also inhibit plasma cholinesterases. Organophosphate poisoning: Lipid soluble, absorbed via skin. Nicotinic and muscarinic effects, CNS and autonomic instability. Miosis, salivation, twitching, agitation, cough, bronchospasm, arrhythmia, seizures, cardioresp arrest, coma, death. Rx: PPE, undress, decontaminate, irrigate eyes, charcoal if ingested <2h; ABC, 100% O2, avoid sux, Toxbase/expert advice, atropine 600mcg-4mg IV every 10-20m until secretions dry up, pralidoxime 2g over 4m 4-6hrly for 7/7, diazepam for seizures/agitation.
Inhalational agents
Halogenated hydrocarbons, halogenated ethers and other (N2O, Xe)
Analgesics
Opioid (natural, semi-synthetic, synthetic)
Non-opioids (simple, NSAIDs (non-selective and selective), anti-neuropathics)
