General Flashcards

Question

Sodium homeostasis (past Q)

Answer 1

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 ```

Answer 2

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

Answer 3

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

Answer 4

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.

Answer 5

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

Answer 6

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

Answer 7

Acromegaly SIADH DI

Answer 8

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

Answer 9

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.

Answer 10

``` 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.

Answer 11

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.

Answer 12

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.

Answer 13

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.

Answer 14

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.

Answer 15

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.

Answer 16

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

Answer 17

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.

Answer 18

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%.

Answer 19

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

Answer 20

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.

Answer 21

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.)

Answer 22

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%.

Answer 23

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

Answer 24

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.

Answer 25

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.

Answer 26

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

Answer 27

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

Answer 28

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).

Answer 29

Inflammatory cascade of cytokines and adhesion molecules Complement and coagulation pathways activated Nitric oxide released in large quantities - vasodilatation

Answer 30

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

Answer 31

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

Answer 32

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).

Answer 33

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

Answer 34

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

Answer 35

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

Answer 36

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

Answer 37

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

Answer 38

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

Answer 39

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.

Answer 40

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.

Answer 41

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.

Answer 42

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.

Answer 43

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

Answer 44

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.

Answer 45

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

Answer 46

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

Answer 47

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.

Answer 48

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?

Answer 49

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)

Answer 50

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?

Answer 51

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.

Answer 52

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

Answer 53

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.

Answer 54

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.

Answer 55

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

Answer 56

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.

Answer 57

``` 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 ```

Answer 58

Synthetic lysine derivative Antifibrinolytic Prevents conversion of plasminogen to plasmin CRASH-2 WOMAN April 2017 - reduces death from PPH by 19%

Answer 59

Isomers Esters and amidesToxicity - which pts at risk? R-bup - cardiotoxic as binds to myocytes and affects mem potential What preservatives used?

Answer 60

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.

Answer 61

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.

Answer 62

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

Answer 63

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

Answer 64

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.

Answer 65

Vaughan-Williams I-IVPhases prolonged = "0, 0+4, 3 and 0"

Answer 66

GABA enhancers- BDZ - Barbituates - Valproate- Vigabatrin (prevents GABA breakdown) Na flux modulators (reduce Na+ influx, stabilising cell mems) - Phenytoin - Carbamazepine Ca channel blockers

Answer 67

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

Answer 68

By receptor: D2, AChE (neostigmine), 5HT4, erythromycin

Answer 69

By receptor: H1, D2, 5HT3, mAChR, steroid Novel - aprepitant - substance P/neurokinin antagonist Non-pharm - acupressure of P6

Answer 70

Inotropes - beta agonists (adrenaline, ephedrine, dobutamine, dopamine, dopexamine) - PDEi (milrinone) - Ca2+ sensitisers (levosimendan, glucagon) - other (digoxin, Ca, thyroxine) Vasopressors - vasopressin - metaraminol - NA - phenylephrine

Answer 71

Crystalloids: hypotonic, isotonic and hypertonic Colloids: natural (albumin) and synthetic (gelatins, starches)

Answer 72

Psychomimetic (ketamine) Psychomotor (cocaine, amphetamines) Respiratory (doxapram) Amphetamines: ADHD, narcolepsy. Deplete NA. Caution++, stop preop.

Answer 73

Antimuscarinics (atropine, glyco, ipratropium, tropicamide) Antinicotinics (muscle relaxants, ganglionic blockers and centrally acting) SEs: lack of fluid everywhere

Answer 74

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.

Answer 75

Halogenated hydrocarbons, halogenated ethers and other (N2O, Xe)

Answer 76

Opioid (natural, semi-synthetic, synthetic) Non-opioids (simple, NSAIDs (non-selective and selective), anti-neuropathics)

Answer 77

Reduce gastric volume (PPI, H2) Prokinetics Barrier - sucralfate Raise gastric pH - citrate

Answer 78

Physicochemical e.g. thio/sux precipitationPharmacokinetic e.g. adrenaline reduces LA absorption Pharmacodynamic e.g. synergism, summation, potentiation, antagonism

Answer 79

WHO classification 1-6; also type A (dose dependent, common, predictable, essentially SEs) and type B (dose independent, uncommon, idiosyncratic, unpredictable, true allergies). Skin prick testing - higher risk, need crash facilities RAST (radioallergosorbent testing) - blood test so low risk. Can get false negatives and does not always correlate with severity of symptoms. Tryptase - time 0, 1-2h, 24h/convalescent.

Answer 80

Polypeptide hormone secreted by beta cells of islets of Langerhans. A and B chains are linked by disulphide bridges. Anabolic effects - glucose and AA uptake, glycogenesis, lipogenesis, protein synthesis. Half life is 5 minutes. Increases activity of the Na/K/ATPase pump, which is how it causes hypokalaemia. By speed of action, or animal porcine/bovine/GM synthetic e.g. Humulin/analogue (latter = GM synthetic, e.g. Humalog) Made by bacteria or yeast - insulin gene inserted into plasmids

Answer 81

Non-genetic: physiological, pathological, pharmacological, hypersensitivityGenetic: polymorphism, inherited conditions

Answer 82

Centrally acting non-opioid analgesic that inhibits reuptake of serotonin, noradrenaline and dopamine. A benzoxazocine. Analogue of diphenhydramine. Antidepressant, antispasmodic and analgesic. Considered similar potency to NSAIDs.

Answer 83

* Steroids - methylpred - inhibit T cell lymphokine production; Cushing's * Calcineurin inhibitors - ciclosporin, tac - prevent T cell activation/cell-mediated immune reactions; nephro/neurotoxic, HTN, DM, hyperkalaemia, enhance NMBs * Antiproliferative - MMF, aza - inhibit T/B cells; myelosuppression, antagonise NMBs, hepatotoxic * Target of rapamycin (TOR) inhibitors - sirolimus - prevent T/B cell activation; HTN, oedema, diarrhoea All increase skin and lymphoproliferative malignancy and predispose to infection.Consider: continuing periop, steroid supplementation, drug levels, bloods for SEs. Steroid production: normally 30mg cortisol/day. Up to 100mg/day in stress for up to 3 days postop. LT steroids means this normal response is absent. Inadequate HPA axis can be demonstrated by Synacthen test - 250mcg IV and observe cortisol surge.

Answer 84

GTN - venodilator via CAMP, reduces intracellular Ca Hydralazine - similar to GTN but more arterial than venous vasodilatation, reflex tachycardia SNP - similar to GTN but both arterial and venous vasodilatation, reflex tachycardia. Red/brown powder, make up with 5% dex. Cover with foil as turns brown/blue with light (cyanide). Produces NO --> increased cGMP --> increased intracellular Ca --> vasodilatation. 0.5-6mcg/kg/min, short half life. Inhibits HPV. Increases ICP. Tachyphylaxis. Cyanide toxicity (tx = O2, hydroxyobalamin, sodium thiosulphate and nitrates).

Answer 85

- Organophosphates (cholinergic): atropine, pralidoxime (& BDZ) - Paracetamol: treat if >150mg/kg ingested/over tx line/staggered. NAC is 150mg/kg over 1h, 50mg/kg over 4h, 100mg/kg over 16h. - Cyanide (pesticides, inhalation, SNP): amyl nitrate, hydroxycobalamin, sodium thiosulphate, dicobalt edetate - Amyl nitrate: methylene blue - CO: O2, hyperbaric O2 - Methanol, ethylene glycol: ethanol, fomepizole - Beta blockers: glucagon, high dose insulin therapy (HDIT), catecholamines - CCBs: CaCl - Opioids: naloxone etc - Serotoninergics: (BDZ), cyproheptadine - Sympathomimetics: (BDZ), ?dantrolene - TCAs: bicarb (if acidotic or QRS>100ms - reduces free drug fraction), hyperventilation, Intralipid, Mg, lidocaine (not phenytoin as Na channel blocker) - Salicylates: RRT, forced alkaline diuresis (bicarb to target urine pH>6.5, serum 7.4-7.5; acidic drug converts to ionic form in the alkaline tubule and cannot be reabsorbed; hypokalaemia is a comp) - LA: Intralipid - NMS: bromocriptine, dantrolene - Iron: deferoxamine - Digoxin: Digibind (digoxin specific antibody fragments) Iron: GI bleed, myocardial dysfunction, coagulopathy, hepatotoxicity Don't forget: RRT: BLAST + others Haemoperfusion (removes larger molecules e.g. theophylline, carbamazepine, paraquat) Activated charcoal

Answer 86

Dissociative anaesthetic and analgesic Dissociation = functional and electrophysiological between the thalamo-neocortical and limbic systemsProduces catalepsy - open eyes, slow nystagmic gaze, intact corneal and light reflexesMay have increased tone and purposeful movement unrelated to painful stimuli EEG - dominant theta activity, alpha wave abolition Enantiomers (S more potent and faster recovery, fewer psych SEs) Induction of GA, analgesic, procedural sedation/analgesia e.g. burns dressings, premed. Useful in trauma/CV-unstable pts, paeds. NMDA non-competitive antagonistAlso acts at mu receptors and reduces glutamate release Analgesic and local anaesthetic pH 4, pKa 7.5 Highly lipid soluble Broken down into norketamine which has 30% activity Onset 30s, distribution half life 10m, elim 3h, VD 3L/kg, PPB 30% 10/50/100 mg/ml IV IM PO IN PR epi CVS: tachycardia, raised BP and CO RS: secretions, bronchodilator, laryngospasmCNS: increases CBF, CMRO2, ICP/IOP Emergence/psych reactions in up to 30% (older, female, higher dose, faster inj; BDZ can reduce). Nystagmus, dilated pupils Opioid sparing, less PONV CI: IHD, increased ICP, porphyria. Can be given to epileptics, no ev incresed seizures.

Answer 87

Mood stabiliser Mimics Na+ and enters cells via fast voltage-gated channels but cannot be pumped out so accumulates intracellularly Reduces the release of neurotransmitters centrally and peripherally Narrow therapeutic range 0.5-1mmol/L Toxicity: tremor, ataxia, dysarthria, GI upset, confusion, seizures. Stop 24-72h preop and take level. >95% renally excreted so watch renal function, care with diuretics Nephrogenic DIHypothyroidism Enhances NMDRs, antagonises neostigmineIncreased risk of NSAID toxicity (PPB) Increased risk of arrhythmia with amiodarone

Answer 88

TCAs: block reuptake of NA and serotonin. Anticholinergic SEs + arrhythmias. Increase resp depressant effect of narcotics. SSRIs: block reuptake of serotonin. No anticholinergic SEs. Fluoxetine is a P450 inhibitor. MAOis: see other card. Stop 2/52 preop. d/w psych re: alternative tx. Stops breakdown of neurotransmitters. Irreversible (phenelzine) and reversible (moclobemide). Cheese rxn = tyramine-rich foods - seizures, hyperpyrexia, coma. ``` Serotonin syn - excess serotonergic activity - altered mentation - neuromuscular hyper-reactivity - autonomic dysfunction Cyproheptadine is serotonin antagonist. ``` Neuroleptic malignant syn - clinically similar to SS but hyperthermia and muscle rigidity predominate.

Answer 89

Long acting synthetic mu receptor agonist Low first pass metabolism High PO bioav - 75% Peak conc within 4h Green liquid Less sedative than morphine Can also give IM/IV Tolerance does develop but slowly Similar GI SEs 90% PPB Metab by liver, excreted urine and bile

Answer 90

Tautomerism - open to closed ring (water soluble to lipid soluble) GABA-A agonist Anxiolytic Indirectly reduces SNS activity 40% oral bioav Procedural sedation, premed, ICU sedation, acute management of agitation

Answer 91

``` ICP monitoring and control Maintain CPP/MAP (MAP>90 if no ICP monitoring) - CPP>60 PaO2>13 PaCO2 4-4.5 Deep sedation +/- paralysis to avoid coughing/vomiting 30 degrees head up Avoid collars/tight tube ties/IJ lines Avoid excessive PEEP Na 145-150 (minimise cerebral oedema; 145-155 if using hypertonic saline) Glu 4-8 Avoid pyrexia Prevent seizures ``` ICP monitoring - GCS (easy but non-specific; unsuitable if sedated) - Imaging (detects focal lesions but requires transfer) - Direct measurement * Bolt (easy, less risk of infection but drift and non-therapeutic) * EVD (therapeutic but harder and risk of infection) Tx raised ICP - General measures - see above - Medical - sedation, osmotherapy (mannitol 0.5g/kg over 15m, aim osm 310-320/3% NaCl 2ml/kg, aim Na 145-155 - Surgical - CSF drainage, evacuation, decompression Other neuro monitoring TCD: blood velocity in MCA. Vasospasm in SAH. SjVO2: fibreoptic oximeter in IJ at jugular bulb level. <60% means low CBF (global perfusion marker) - no. of desats relates to outcome NIRS: two oximeter probes on scalp. Non-invasive. Normal 60-80%. Brain tissue O2 sensor: in a modified bolt. Normal 3.3-4kPa Micro-dialysis catheter: lactate, pyruvate and glucose diffuse out and are measured. Rising lactate/pyruvate ratio is sensitive and occurs before ICP rise

Answer 92

``` Affects up to 80% ICU pts Acute onset, fluctuating course Altered consciousness Reduced attention Hyperactive, hypoactive, mixed ``` Increases morbidity, mortality, LoS, days of MV, persistent cognitive impairment and PTSD Each additional day spent in delirium is associated with a 20% increased risk of prolonged hospitalisation and a 10% increased risk of death. RFs - Patient: elderly, depression, alcohol, HTN, smoking, sensory or cognitive impairment - Illness: anaemia, acidosis, metabolic disturbance, hypotension, sepsis, trauma, emergency surgery, high APACHE score, pain - Environmental: MV, sleep deprivation, immobilisation, drugs (opiates, steroids, BDZ, anticholinergics) ``` Mx Non-pharmacological - Support and orientation - Attention to environment - Correct sensory impairment - Address organic causes (pain, hypoxia, hypercapnoea, acidosis, infection, drugs) ``` Pharmacological - Haloperidol first line. Dose variable according to age, CV statis, degree of disturbance. 0.5-2.5mg enterally/IV. If still unmanageable 20m post IV dose, double dose. Then QDS regular followed by wean. Daily 12 lead ECGs for QTc. May need procyclidine for EPS. - BDZ - first line for BDZ or EtOH withdrawal. Second line rescue for rapid tranquilisation if haloperidol failing and pt/others in danger. - Quetiapine - Clonidine and dexmedetomidine

Answer 93

``` Na+ restriction Diuretics BBs for portal HTN TIPSS OLTx ```

Answer 94

``` ABCDE Exclude the lethal trial - acidosis - ABG - hypothermia - temp - coagulopathy - ACT, TEG, formal FBC/coag Echo Surgical review ```

Answer 95

Type 1: polymicrobial (average 4 orgs) - accounts for 70%, better outcomes Type 2: group A strep +/- staph Type 3: Vibrio spp Type 4: Candida ``` Features 'Dishwater pus' Beneath dermis Late skin changes Disproportionate pain LRInec score - Low Risk Indicator for Nec Fasc Rx Taz + clinda ``` Between SC fat and deep dermis (unlike cellulitis, which is between dermis and epidermis) RFs immunosuppression, DM, ca, trauma, IVDU, alcoholic ``` Tx Surgical debridement Micro discussion + abx e.g. ben pen/clinda/gent IVIg Plastics r/v ```

Answer 96

FFP: all clotting factors. Its INR is 1.6 so it cannot lower INR below this. Dose 15ml/kg. Must be ABO compatible, preferably matched. Group A universal. (RhF doesn't matter). 150-300ml. Stored at -25 for 3y. Ok for 24h at 4C, 4h at room temp/unknown. Cryo: fibrinogen + vWF + factor 8. Dose 2 pools (adults). Each unit 50ml, a pool is 100-250ml. Stored below -25 for 3y. Ok for 4h at room temp. Group A universal. Target >1.5g/L; 2 pools raises fib by 1. A freeze-dried preparation of fibrinogen alone also exists. PCC: specific, limited clotting factors (2/7/9/10 + protein C/S). Freeze-dried. Smaller volume, quick to give, expensive. Warfarin reversal. IVIg: Igs are glycoproteins produced by plasma cells. Derived from plasma of >1000 blood donors. Provides a broad range of abs to the diverse pathogens to which the cohort have been exposed. Risk of VTE, AKI and anaphylaxis. PRC 250-350ml, 2-5C, 42d max HCt 0.5-0.7 Raises Hb by 10 Plts Room temp, up to 300ml By centrifugation of whole blood units, or by apheresis (single donor) Do not have to be ABO matched but better increment if they are (10-20%) (small amount of plasma in unit). O to receive O. Group A universal. Raises plt by 20

Answer 97

``` CT head <1h Initial GCS <13 in ED GCS <15 2h post-injury Post-traumatic seizure Focal neurology Suspected open or depressed skull fracture Evidence of basal skull fracture (haemotymanum, panda eyes, CSF leak) Vomiting > 1 episode Retrograde amnesia >30 minutes ``` ``` CT head <8h Age >65 Bleeding/clotting disorder or warfarin Dangerous mechanism Retrograde amnesia >30m ``` ``` CT C-spine <1h Initial GCS <13 in ED Intubated Plain X-rays technically inadequate Plain X-rays abnormal or suspicious Pt having scan of other areas Canadian C-spine rules - age >65 - dangerous mechanism - focal neurology or parasthesia ``` ``` Neurosurgical discussion/referral Acute intracranial lesion on CT Persistent GCS<9 post resuscitation Unexplained confusion >4h Deteriorating GCS Progressive neurology Seizure without full recovery Penetrating injury CSF leak ``` Intubation - immediate - Airway unprotected/loss of reflexes - PaO2<13, PaCO2>6 or <4 - Irregular respiration - GCS 8 or under Intubation - pre-transfer - Deteriorating GCS (1 or more in motor score) - Unstable facial fractures - Intra-oral bleeding - Seizures

Answer 98

- Permissive hypotension* - Haemostatic  resuscitation - Damage control surgery *Traditionally SBP 80-100, but as perfusion more important than pressure, consider MAP>65 with good radial pulse (= SBP about 80) and good pulsox waveform. If BP too high, titrate aliquots of fentanyl to provide sympatholysis as well as analgesia.

Answer 99

Clinically significant bleeding and fib<1.5 (2 in obstetrics) Pre-procedure and fib<1 Bleeding a/w thrombolytics Inherited hypofibrinogenaemia and no fib concentrate available (1u will raise fib by 0.5g/L)

Answer 100

Coeliac trunk SMA IMA

Answer 101

Hypovolaemic: small LV, hyperdynamic Obstructive: dilated RV in PE, RV collapse in tamponade, IVC dilation Distributive: hyperdynamic LV though good LV size Cardiogenic: dilated LV, hypokinetic, IVC dilated

Answer 102

Rare, life-threatening Presents like HUS but treatable with PLEX so need to differentiate (they can also co-exist) vWF is made in large multimers, normally cleaved by the protease ADAMTS13 In TTP, IgG abs form against ADAMTS13 so ultra-large vWF accumulates Plts aggregate and clump --> microthrombi occluding the microcirculation, MAHA, MOF Classic pentad: fever, MAHA, thrombocytopenia, AKI, neurological features (seizures, ICH, focal deficits) TTP = neuro>renal, HUS = renal>neuro RFs: E.coli 0157, preg, CTDs, GvHD, ca Ix: haemolysis (blood film, low haptoglobins, high LDH, high retics, unconj. bil), AKI, anaemia, low plts, ADAMTS13 protease low, biopsy of skin/muscle/LN/BM shows microaneurysms Tx: PLEX ASAP with FFP/cryo replacement (not HAS), >1.5 plasma vols/day until plt>150 and LDH normalising; steroids 1mg/kg/day; don't transfuse unless clinically indicated e.g. haemorrhage. Plts are CI. Methylpred after first exchange Consider LMWH when plt>50 Rituximab as rescue therapy

Answer 103

Most have inherited ADAMTS13 mutations or acquired abs against it Types: D+HUS (>90%) and D-HUS (atypical) - latter worse prognosis D+: E.coli 0157, Shigella D- or aHUS: Strep pneumo in 40%; also pregnancy, drugs e.g. tac/cic, transplant, HIV Features: bloody diarrhoea + classic pentad of TTP/HUS (fever, MAHA, thrombocytopenia, renal and neuro) Ix: haemolysis, AKI, low plts, anaemia; bx thrombotic microangiopathy; genetic testing, low C3 Tx: PLEX ev base less certain than for TTP; no ev for steroids, supportive, plts are CI, avoid abx if possible as worsen toxin production, tx underlying cause

Answer 104

Occurs in otherwise healthy people Diagnosis of exclusion 2 forms: acute (immune complexes) and chronic (IgG abs) Petechiae, purpura, rarely clinically significant haemorrhage

Answer 105

``` PET/eclampsia HELLP - plt <100, AST>70, LDH>600 AFLoP HUS/TTP SLE Sepsis ```

Answer 106

``` DCM - PPCM, alcohol RCM HCM ARVCM Takotsubo - apical ballooning as that is where sympathetic fibres concentrated ```

Answer 107

- MCA territory stroke of >50% on CT - Perfusion deficit of >66% on CT - Infarct volume >82 mL within 6h or >145ml within 14h on MRI Trials: DESTINY 1/2, DECIMAL, HAMLET Age <60 - reduced mortality with hemicraniectomy <48h of onset Postop severe disability very common in <60s but universal in >60s

Answer 108

Based on risk/reality of acute brain oedema vs. risk of osmotic demyelination (CPM) Classify by severity (down to 130, down to 125, <125) and onset (< or >48h) rather than clinical fluid status which is not sensitive or specific. Tx in first hour of moderate-severely symptomatic hyponatraemia, regardless of acute/chronic: - 150ml 3% hypertonic saline over 20m - Check the sodium whilst repeating the bolus - Repeat the above twice or until a rise of 5mmol/L achieved - If clinically improved, shift focus to tx of underlying cause; allow rise of 10mmol/first 24h and 8/24h thereafter; check at 6/12/24h thereafter - If not clinically improved, continue hypertonic saline and aim for 1mmol/L/h rise; continue until clinical improvement, rise of 10mmol/L or Na up to 130; measure Na 4hly; consider alternative causes for symptoms Symptoms Moderately severe: nausea, confusion, headache Severe: vomiting, seizures, GCS<8, cardiorespiratory distress Extremely low urine osmolality (<100) - Primary polydipsia - Low solute intake - Beer potomania (exclusive beer diet low in solutes --> impaired free water clearance due to loss of urea concentrating gradient)

Answer 109

Hangman's: hyperextension. C2 pars interarticularis bilaterally + usually slippage of C2 on C3 Jefferson: axial load. C1 burst fracture Odontoid peg/process (aka dens) Clay-Shoveler's - posterior spinous process, stable, incidental

Answer 110

>11g/L predicts the pt to have portal HTN, with 97% accuracy - "transudate" <11 predicts no portal HTN - "exudate"

Answer 111

Sectioning: need 3 people - AMHP or nearest relative, section 12 approved Dr and registered medical practitioner e.g. GP. Section 2: 28d. For hospital assessment and tx. Usually first episode. Cannot renew but can transfer to S3. Section 3: 6m. Pt already known to MH services. Section 4: 72h. 1 Dr + 1 AMHP. Emergency. Section 5: to prevent pt leaving hospital; only if S2/3/4 not possible. - 5.2 Doctors' holding power - 72h - 5.4 Nurses' holding power - 6h (RMN only) Cannot refuse tx under section except on section 4/5 or for ECT.

Answer 112

Primary - Addison's, haemorrhage, ca, infection etc Secondary - pituitary failure Tertiary - exogenous steroid suppression Adrenal insufficiency in acute illness (American College of CCM) - random cortisol <10, or change <9 with 250mcg synacthen. Steroids improve shock but unclear whether mortality benefit. Consider in vasopressor-dependent shock - 200mg hydrocort/day for at least 7d.

Answer 113

Systolic - impaired contractility. Always accompanied by diastolic dysfunction. Diastolic - impaired filling due to impaired relaxation and/or stiff ventricle. Can occur alone. e.g. HTN, valvular disease, RCM.

Answer 114

Persistent air leak >24h post chest drain Surgical, procedural, spontaneous Rx usually conservative/tx underlying lung disease Aim to minimise transpulmonary pressure gradient by lowering RR, Vt, reducing I:E, applying least amount of chest drain suction possible, wean from MV asap.

Answer 115

Life-threatening condition characterised by acute refractory bradycardia progressing to asystole and one or more of: - metabolic acidosis - rhabdomyolysis - hyperlipidaemia - fatty infiltration of liver Mechanism poorly understood - ?impaired mitochondrial fatty acid metabolism ``` RFs/associations High dose/long duration propofol (>4mg/kg/h for 48h) Acute neuro injury Low carb intake Catecholamine infusion Steroid infusion ``` Other features Increasing inotrope requirement/CVS collapse Green urine/hair Ix Bloods: lipaemic serum, lipids, renal failure, high CK, deranged LFTs, hyperkalaemia ABG: unexplained lactic acidosis ECG: Brugada-like, arrhythmia, heart block ``` Mx Stop propofol immediately Supportive Consider pacing Adequate carb intake Carnitine (theorectical) Haemodialysis/haemoperfusion ECMO ```

Answer 116

Aims Determining and treating the cause of cardiac arrest Minimising brain injury Managing cardiovascular dysfunction Managing problems that may arise from global ischaemia and reperfusion injury ``` Actions Hx/ex/ix Advanced airway, LTVV, SpO2 94-98% PaCO2 4.5-5 Cardiac enzymes, ECG/echo +/- cath (esp initial rhythm VT/VF) +/- IABP TTM if not waking - 36C for 24h (anticipate cold diuresis) Especial avoidance of hyperthermia >72h Sedation and NMB Electrolyte/fluid mx Inotropic support - MAP>80 Lines + CO monitoring ScvO2 >70%, Hct >30% Normoglycaemia General ICU care Neuroimaging + other indicated imaging when stable Consider EEG Secondary prevention Glu<10 CTH only if primary neuro event suspected; otherwise cath lab ``` Prognostication: an approach (Resus Council 2015) - Wait 72h post rewarming - Exclude confounders - esp sedatives If unconscious and M1-2 at 72h, - Absent pupillary/corneal reflexes and/or - B/L absence of N20 SSEP median nerve Poor outcome very likely. If not, wait at least 24h then 2 or more of: - Status myoclonus <48h post ROSC - High neuron-specific enolase (>33) - Unreactive burst-suppression or status epilepticus on EEG - DAI on neuroimaging Then poor outcome very likely. If not, indeterminate; observe and reassess.

Answer 117

The posteromedial papillary muscle is more likely to rupture, causing flail of the anterior valve leaflet. (The anterolateral papillary muscle may be more protected from rupture by a dual blood supply from both the left anterior descending coronary artery and from the circumflex coronary artery.) Tx drugs, IABP

Answer 118

Mannitol 20% 0.25-1g/kg over 15m Onset mins, duration 3h Draws water across BBB and slows rate of CSF production Can cause rebound raised ICP as eventually crosses BBB Risk of dropping CPP via resultant diuresis ``` Hypertonic saline 3% 3ml/kg over 10m Onset mins, duration 1h Less likely than mannitol to produce hypovolaemia Target Na 145-155 Risk of hyperchloraemic acidosis Central administration only ```

Answer 119

``` PVL is a specific Staph aureus toxin Causes leucocyte destruction and tissue necrosis Rapid lung cavitation and MOF Post-influenza pneumonia Soft tissue infections Clinda/linezolid + rifampicin IVIg d/w micro and resp ```

Answer 120

Rate 25-35ml/kg/h with post-dilution (need higher for pre-dilution) Ammonia/cytokine/myoglobin removal - indications for higher dose RRT Blood pump rate 250-300ml/min Fluid balance aim per hour or 24h Anticoagulation strategy (consider none if INR>2 or plt<60) Dialysis - tea bag Filtration - coffee filter Classic renal indications - Hyperkalaemia - Acidosis - Fluid overload - Uraemia with complications Non-renal indications - Fluid balance management - Toxin removal - drugs, ammonia - Correction of electrolyte disturbance - Temperature control - Removal of inflammatory mediators in sepsis

Answer 121

Trauma, burns, crush injury, compartment syn, MH, exercise, statins, cocaine, amphetamines, serotonin syn, NMS, phaeo, thyroid storm End result is failure of the myocyte Ca-ATPase pump. Increase in sarcoplasmic Ca causes unopposed muscular contraction. Intracellular proteases are activated and muscle breakdown occurs. Substances are released into blood (H+, K+, lactate, myoglobin, uric acid, PO4). Comps: AKI, hyperkalaemia, hypocalcaemia, DIC. Ix: urinary myoglobin. Tx: treat cause, fluid resuscitation, forced alkaline diuresis (bicarb boluses 50-100mmol to achieve pH 6.5; UO >3ml/kg/h or 300ml/h). Myoglobin is filtered, CK is not (RRT)

Answer 122

``` CVP 8-12 MAP>65 UOP >0.5 ScvO2>70 or SvO2>65 HCt>30 ```

Answer 123

50% initially missed 3x more common on left 100% need surgical repair

Answer 124

``` High K/PO4/uric acid Low Ca AKI from uric acid and CaPO4 crystals Metabolic acidosis Lactataemia Clinically: GI upset, weakness, parasthesia, tetany, arrhythmias, oligoanuria Response to chemo/radio/steroids Time lag 12-72h ``` RFs: high tumour burden, sensitive tumour, extensive BM involvement, chemo, haem malignancy Prevention: hydration, allopurinol (xanthine oxidase inhibitor - prevents uric acid formation), monitor electrolytes Tx: urate oxidase or rasburicase (recombinant urate oxidase) Avoid overtreating the low Ca as just makes more crystals and AKI worse

Answer 125

Normal 5-7. IAH >12. ACS >20 with new organ failure. Primary - intra-abdominal disease Secondary e.g. fluid overload, leaky capillaries Recurrent Effects Resp - reduced FRC, V/Q mismatch, high Paw CVS - IVC compression, reduced preload, raised CVP, cardiac dysfunction Renal - ischaemia Neuro - raised ICP Abdo perfusion pressure APP = MAP - IAP Intravesicular pressure measurement (can also use gastric, colonic, uterine) Need 25ml fluid in bladder Manometer or pressure transducer Measured at end expiration with pt supine (abdo wall muscles relaxed) Measure every 4h Tx Cautious fluid resuscitation, pressors/inotropes, sedation/analgesia/muscle relaxation, treat cause; NG decompression/prokinetics/enemas, remove tight dressings, diuretics, RRT Surgical decompression with delayed closure (open abdo/laparostomy/Vac dressing) - for primary ACS or refractory secondary ACS

Answer 126

SJS - <10% BSA skin detachment TEN - >30% 10-30% = SJS/TEN overlap. Rash DD - Infective - local (cellulitis/nec fasc), systemic (septicaemia) - Autoimmune e.g. pemphigoid - Drug reaction inc. SJS/TEN spectrum TEN diagnosed by exclusion of other causes and punch bx. Causes of TEN: most commonly drugs e.g. abx/immunosuppressants/anticonvulsants/NSAIDs; esp new/high dose drugs. Next most common are infections, esp Mycoplasma in children. HIV is a major risk factor (100x increased risk). Cancer is associated. Certain HLA types also associated. Tx remove precipitant, IVIg, possibly immunosuppression. Reverse barrier nursing. Nutrition. Fluids. Comps - akin to burns - fluid/heat loss, infection, hypercatabolism. Mucosal involvement. Target lesions. Mortality - SCORTEN scale. Age, associated ca, HR, urea, skin condition, bicarb, glucose.

Answer 127

DD: malaria, septic shock, CNS infection, VHF, TTP GI features + consumptive coagulopathy + septic shock ``` Isolation in negative pressure room PPE Escalation to named consultant D/W public health lead for hospital - ID/micro Cover for sepsis and malaria Refer to Ebola specialist centre Contact tracing Ix: ELISA/PCR ```

Answer 128

Falciparum/vivax/ovale/malariae Incubation 2/52 Initial sx nonspecific Comps: cerebral malaria, hypoglycaemia, acidosis, AKI, ARDS Thick and thin films Chloroquine, quinine, artesunate Quinine causes more hypoglycaemia and prolongs QTc Severe: glu<2.2, Hb<50, bicarb<15, parasitaemia>2%, lac>5, creat>265

Answer 129

Presentation of bowel obstruction in the absence of a mechanical cause Acute - critical illness, postop, trauma, spinal anaesthesia, renal transplant, C.diff Chronic - neuro, CTDs, infection, paraneoplastic Rx conservative, NBM, fluid/electrolytes, tx cause, neostigmine, endoscopic decompression, surgical decompression, nutritional support

Answer 130

Thiamine deficiency Occurs in Asia (rice diet) Dry - neuro manifestations Wet - high output heart failure

Answer 131

Tx: neuraminidase inhibitors eg oseltamivir 75mg BD PO (A and B), adamantanes eg amantadine (only active against flu A). High risk: >65, NH resident, malignancy, comorbidities, immunosuppression, pregnancy/postpartum Treat on suspicion, do not wait for confirmation Most effective in first 48h Comps: influenza pneumonia, secondary bacterial pneumonia (classically Staph), myositis/rhabdo, CNS involvement eg encephalopathy/encephalitis/transverse myelitis/GBS, pericarditis, TSS Average 2 days incubation, 5 days shedding Fever, headache, myalgia, malaise + manifestations of respiratory tract illness/coryza

Answer 132

1. Wrong site surgery - a surgical intervention performed on the wrong patient or wrong site 2. Wrong implant/prosthesis 3. Retained foreign object post-procedure (i.e. cvc line and guidewires) 4. Mis-selection of a strong potassium containing solution 5. Wrong route administration of medication 6. Overdose of Insulin due to abbreviations or incorrect device 7. Overdose of methotrexate for non-cancer treatment 8. Mis-selection of high strength midazolam during conscious sedation 9. Failure to install functional collapsible shower or curtain rails (mental health) 10. Falls from poorly restricted windows 11. Chest or neck entrapment in bedrails 12. Transfusion or transplantation of ABO-incompatible blood components or organs 13. Misplaced naso- or oro-gastric tubes 14. Scalding of patients (due to water for washing/bathing only) 15. Unintentional connection of a patient requiring oxygen to an air flowmeter 16. Undetected oesophageal intubation (temporarily suspended)

Answer 133

dV / dP Normal: 100-200ml/cmH2O (adults - lung and chest wall are each 200), 2.5-5ml/cmH2O (children) Normal on MV: 50-100ml/cmH2O Low: restrictive lung disease, ARDS, obesity, airway obstruction, PTX, atelectasis, bronchospasm. Need small, rapid breaths to reduce WoB High: obstructive lung disease; emphysema, asthma. Need large, slow breaths to reduce WoB Static: measured during plateau pressure (end inspiration) during absence of airflow. Dynamic: measured at a given intrathoracic pressure at any point in the respiratory cycle. At low frequencies in normal lungs, there may be little difference between static and dynamic. At higher frequencies, dynamic is lower because of incomplete alveolar filling in the time available. Dynamic compliance = Vt / (Ppeak - PEEP) Static compliance = Vt / (Pplat - PEEP)

Answer 134

Physio technique using 'Bird' machine (Dr Forrest Morton Bird) Pneumatically driven device Increases Vt, improves gas exchange, reduces WoB, improves secretion clearance CI in undrained PTX, CVS instability, raised ICP Risks: air swallowing, lung injury, reduced venous return

Answer 135

Artificial Manual Breathing Unit!

Answer 136

Manual - Percussion - Vibration - Positioning and postural drainage - Mobilisation/exercise - Deep breathing exercises ``` Machine-assisted - Manual/ventilator hyperinflation - Mechanical in/exsufflator (aka cough assist - +ve pressure then rapid switch to -ve pressure stimulates strong cough) - Intermittent positive pressure breathing (Birding) - Incentive spirometry - Suctioning +/- saline instillation ```

Answer 137

Aim: reduce/prevent atelectasis, improve secretion clearance, especially postop Mimics sign or yawn - increases lung volume and recruits atelectatic areas Patient expires normally, breathes in slowly and deeply for as long as possible, holds breath for 5-10s then expires normally Device gives visual feedback (pt aims to reach goal marker, whilst keeping flow indicator in range) Pt needs to be motivated and have good technique Example regime 10 breaths QDS with coughing after each session

Answer 138

Non-dihydropyridines most lethal Bind to L-type calcium channels, preventing intracellular influx of Ca Effects: - CVS (bradycardia, hypotension, heart block, myocardial depression, low SVR; can progress to refractory shock and death; myocardial and mesenteric ischaemia) - Metabolic (hyperglycaemia and hypoinsulinaemia as insulin release is dependent on Ca influx into islet beta cells). Degree of hyperglycaemia correlates with severity of toxicity. Tx ABCDE Fluid resuscitation Activated charcoal within 1h/4h if MR Temporising positive chronotropes - atropine Calcium gluconate 60ml 10%, consider infusion Invasive lines Vasopressor/inotropic support (depending on whether poor contractility or vasoplegia predominant feature) HIET - High dose Insulin Euglycaemic Therapy Consider Intralipid CO monitoring and echo VA ECMO rescue HIET - Start with glucose bolus 50ml of 50% (unless glu>22), and insulin bolus 1u/kg to saturate receptors - Insulin infusion 0.5u/kg/h (titrated to max 5u/kg/h) + concurrent glucose infusion to maintain glucose 5.5-14 (may need large vols so 50% via CVC preferable) - Monitor glu and K - Wean after other vasoactive agents off - Goals: HR>60, SBP>90, reversal of conduction abnormalities, UO>1-2ml/kg/h, resolution of acidaemia, improved contractility, improved mentation, euglycaemia - Mechanisms: Increases glucose uptake by myocytes - improves cardiac function Permits Ca entry into mitochondria Increases PDH activity so improved lactate clearance

Answer 139

Type 1 - benign, non-immune, mild, self-limiting, plts rarely <100, occurs in up to 30% Type 2 - what we really mean when we say HIT. Occurs in 1-5% with UFH, <1% LMWH. PF4-heparin complex triggers immune response, plt activation/aggregation, thrombosis. Only a small proportion of pts with abs develop clinically relevant HIT. Plts usually 40-80. D5-10. Ix: PF4-heparin abs. IgG most sensitive. Functional assays eg HIPA (heparin-induced platelet activation) or serotonin release assays Comps: venous/arterial thrombosis, DIC, necrosis at injection sites, may have anaphylactic reaction to heparin bolus, death Rx: stop all heparin, including locks/coated catheters/circuits; avoid plt transfusion; do not wait for lab confirmation; alternative anticoag Alternatives - Direct thrombin inhibitors (bivalirudin, lepirudin) - Factor Xa inhibitors (fondaparinux, danaparoid)

Answer 140

Infection: sepsis, TB, HIV, malaria, CMV, IMN Malignancy: leukaemia, lymphoma, metastatic ca Drugs: HIT, abs, anticonvulsants, chemo, alcohol Iatrogenic: extracorporeal circuits Haem: DIC, ITP, massive transfusion Hepatic dysfunction: cirrhosis, HELLP Autoimmune: SLE, RA, APLS, TTP, ITP Pseudo (plt clumping) Hypersplenism, B12 def

Answer 141

Often benign except in elderly/low CVS reserve NB propranolol - Na channel blockade + QRS widening so give bicarb Sotalol - K efflux + long QT - beware TdP Bradycardia, hypotension, heart block, heart failure. Bronchospasm, hypoglycaemia, hyperkalaemia, seizures. ``` Tx ABCDE Fluid resuscitation Beta agonists, positive chronotropes, vasoactive agents, pacing Treat K / hypoglycaemia Activate charcoal within 1h Glucagon 50mcg/kg up to 10mg -> 2-10mg/hr (traditional option but inferior to HIET) HIET Consider Intralipid VA ECMO ```

Answer 142

Protein that controls interaction of actin and myosin to bring about cardiac myocyte contraction. I, T, C Cardiac conditions MI (type 1/2), myo/peri/endocarditis, CM, cardiac contusion, heart failure, cardiac surgery, PCI, arrhythmia, DCCV, valvular disease, cardiotoxic drugs Non-cardiac conditions Sepsis, PE, renal impairment, critical illness, burns, stroke, SAH In MI: rise by 4-8h, peak 18-24h, stays up for 10 days Raised trop is independently associated with increased ICU LoS, and increased mortality in ACS. More specific than CK-MB which is also in skeletal muscle etc. Pros: widely available, familiar, predictive of outcome/mortality, AUC correlates with infarct size, highly sensitive Cons: non-specific, hard to interpret in renal failure, washout occurs post reperfusion, can't detect early reinfarction, different reference ranges for different assays, often need serial values to interpret

Answer 143

Neoplastic proliferation of immunoglobulin-producing plasma cells Presentation related to - infiltration of bone marrow (symptomatic anaemia, bone pain) - renal damage from light chains - hypercalcaemia - immune dysfunction Ix: SPE, serum free light chain assay/BJP, BM aspiration/bx (at least 10% clonal plasma cells), PET CT/MRI, cytogenetics Differentials: MGUS, amyloidosis, metastatic ca, smoldering MM, Waldenstrom's macroglobulinaemia Tx - BMT (autologous for slowing of progression is standard of care in fit <65s, few are eligible for potentially curative allogeneic tx; harvesting/apheresis done pre-chemo) - Chemotherapy varies according to BMT eligible/non-eligible; induction and maintenance - Variable prognosis depending on risk stratification (pt factors, cytogenetics); almost all relapse

Answer 144

Chronic multi-system autoimmune disease Young females Polyclonal B cell secretion and formation of immune complexes (type 3 HS) May be triggered by EBV Hx: relapsing/remitting, malaise, fatigue, myalgia, fever, wt loss, joint pain, rash Ex: skin, joints, mucous mems, ulceration, alopecia, peri/myo/endocarditis (Libman-Sacks), Raynaud's, IHD, VTE, pul fibrosis, effusion, cranial/peripheral nerve lesions, transverse myelitis, psychosis, GN and renal failure, hypercoagulable, APLS Ix: anaemia, low plts, coagulopathy, renal impairment, CXR, echo, antibodies Diagnostic criteria (4 or more) - Malar (butterfly) or discoid rash - Photosensitivity - Oral ulcers - Non-erosive arthritis - Serositis: pleuritis, pericarditis - Renal: proteinuria, casts - CNS : seizures, psychosis - Haem: haemolytic anaemia, leucopenia, thrombocytopenia - Immune: anti-dsDNA, anti-smooth muscle antibody, anti-phospholipid antibody, ANA Tx Symptomatic/supportive: topical steroids, sunblock Specific tx: hydroxychloroquine, steroids, aza, methotrexate, MMF, cyclophosphamide, rituximab if B cell deplete ICU relevance Immunosuppressed, skin care, VTE risk, renal injury risk, adrenal suppression, haem abnormalities, restrictive lung disease

Answer 145

Correlates with increasing age, but is not an inevitable consequence of ageing 10% of >65s, 25% of >85s Dynamic and potentially reversible More than simply the combination of disability (functional impairment) and the presence of comorbidities Results in adverse health outcomes (death, disability, dependency and falls) and high costs Critically ill frail pts have much worse outcomes than non-frail matched controls Fried's definition: frailty phenotype 3 or more of 5: weakness (reduced grip strength), slowness (walking speed), low physical activity, self-reported exhaustion, unintentional weight loss (>4.5kg/y) RFs: age, genetics, lifestyle, comorbidities, environment Mx - MDT with specialist geris - PT/OT - Review of medications - Early ax/tx comps of acute illness e.g. delirium, falls, pressure sores - Nutrition - Early discussion of end of life goals

Answer 146

Deaths in pregnancy/up to 6/52pp Mortality rate 8.5 in 100, 000 ``` Direct (directly related to pregnancy/delivery) 1. VTE 2. Psychiatric 3. Amniotic fluid embolism (then haemorrhage, sepsis, PET) ``` Indirect 1. Cardiac disease (and biggest cause overall) 2. Neurological disease 3. Sepsis MBRRACE messages for critical care - Early recognition of critical illness and MDT involvement is key - Altered LOC is a red flag, not an early warning sign - Key ix should not be delayed due to pregnancy - SRF should trigger early ECMO referral - Obstetricians/obstetric anaesthetists should be involved with women on ICU with hypertensive disorders of pregnancy - ICU staff must be involved in any RCA/SCR/SUIs from maternal deaths RFs for maternal death - Low SE status - Ethnic minority - Late booker/poor attender - Obesity - Domestic violence - Substance abuse AFE - phase 1 - SOB, cough, CV collapse, hypoxia - phase 2 - DIC Precipitous labour, grand multipara, PET, IOL, older

Answer 147

RFs: obesity, (G)DM, immunosuppressant drugs, anaemia, previous pelvic infection, PV discharge, hx group B strep, invasive procedures (amniocentesis, cerclage), PROM Sources Obstetric: chorioamnionitis, septic abortion, wound infection (LSCS/epis), mastitis Non-obstetric: pyelo, nec fasc, pneumonia, septic thrombophlebitis, DVT Orgs a/w death: E.coli, group A strep Orgs of chorioamnionitis: mixed Gram pos/neg

Answer 148

``` Guanosine analogues - aciclovir Poor PO bioav Gets incorporated into viral DNA - terminates replication Gancyclovir is effective against CMV Neuro SEs ``` Neuraminidase inhibitors - oseltamivir Prevents release of new virions Good PO bioav N+V Both groups renally cleared

Answer 149

Fungi - Yeasts - solitary cells that reproduce by budding e.g. candida - Moulds - exist in long filaments (hyphae) which grow by apical extension e.g. aspergillus Important medical fungi: candida, aspergillus, cryptococcus, PJP RFs: HIV/AIDS, solid organ or stem cell transplants, cancer, immunosuppressed, institutionalised, neonates, poor housing conditions, long ICU stay, burns, major surgery, DM, TPN, renal failure and HD, high APACHE score, pancreatitis, broad spectrum abx, presence of a CVC, IVDU Antifungals - Azoles (e.g. fluconazole; tx candida; disrupts fungal mem) - Polyenes (e.g. amphotericin B, nystatin; tx candida, aspergillus, cryptococcus; creates pores in fungal cell walls) - Echinocandins (e.g. caspofungin; tx candida; inhibit cell wall synthesis) ``` Fluconazole 100% PO bioav Penetrates BBB (the only antifungal that does) Enhances warfarin effect Inhibits steroid synthesis ``` Amphotericin B Parenteral only, poor BBB penetration SEs: renal impairment in 80%! N+V, myalgia, rigors, thrombophlebitis, seizures Caspofungin/anidulafungin Semi-synthetic Parenteral only, poor BBB penetration Fewer SEs but can cause deranged LFTs, GI sx and delayed hypersensitivity None of the antifungals need dose adjustment in renal failure. Surgery may be required e.g. fungus ball. ``` Ix - Culture from blood/other fluid/swabs: gold standard but hard to grow (only +ve in 50-70% and takes days) - DNA PCR - Antigen testing Galactomannan antigen - aspergillus Cryptococcus capsular polysaccharide Histoplasma antigen β-d-glucan - non-specific - India ink stain for cryptococcus ``` Invasive candidiasis - mortality 60% untreated, 40% treated Complications: haematogenous spread causing endocarditis, ocular involvement/endophlathmitis, meningitis, osteomyelitis (most often vertebral). All pts must have fundoscopy and echo.

Answer 150

1.5 per 1000 pop Retrovirus of lentivirus subgroup HIV-1 and 2 (latter milder and almost exclusively West Africa) Transmission: sexual, vertical (up to 30% in preg, 20% BF), infected needles, infected blood products/organs At risk: promiscuous individuals, co-infection with other STIs, IVDU, haemophiliacs, central/west African pop ``` Major OIs: Bacterial: TB, Strep pneumo, H. influenzae Viral: CMV, VZV Fungal: PJP, candida Protozoal: toxoplasma, cryptosporidium ``` Contain reverse transcriptase - allows viral RNA to be transcribed into DNA, which is incorporated into host cell genome. Preferentially infects T-helper cells (CD4) and destroys them - pt becomes susceptible to OIs and cas. Natural hx - Acute seroconversion illness - Latent period/asymptomatic infection - median time to AIDS 10y (untreated) - AIDS when CD4<200 or AIDS-defining illness; advanced AIDS when CD4<50 Diagnosis P24 antigen - early Otherwise PCR after 3/12 window (A few) AIDS-defining illnesses - HIV wasting syndrome - PJP - Chronic HSV - Candidiasis of oesophagus/bronchial tree - Kaposi's sarcoma - Toxoplasmosis - CMV retinitis - Cryptococcal meningitis HAART - Protease inhibitors - Reverse transcriptase inhibitors (nucleoside/tide analogue or non-nucleoside) - Integrase inhibitors - Entry inhibitors - Usual regime 3 agents - aim to achieve undetectable viral load by 4-6/12; can achieve near normal life expectancy - Start when CD4<200 to reduce risk of OI - Start if presenting with OI, within 2/52 of antimicrobials - Starting sooner reduces rate of progression to CVS/neuro disease (<350) - SEs liver/renal dysfunction, GI sx, lactic acidosis, dyslipidaemia/IHD, pancreatitis, rash (inc SJS/TEN), hypersensitivity rxns, peripheral neuropathy. Many are P450 inhibitors. - Almost all are enteral - poor absorption can --> drug resistance. Zidovudine is only IV drug. No ev that GA alters disease process in terms of immunology. HIV pts on ICU: 30-40% mortality overall. Half are unrelated to the HIV. 1. Respiratory. Acute respiratory failure most common reasons for admission; PJP in up to 50% of these. PTX in PJP on MV = poor prognostic sign. BAL gold standard diagnostic. Co-trimoxazole, pentamidine + steroids. Bacterial pneumonia next most common; consider empirical cover for Pseudomonas and Staph aureus. 2. Neurological. Intractable seizures or low GCS. Differentials = infective (toxo most common, cryptococcus, HSV) or non-infective (cerebral lymphoma, PMLE). Nearly 70% mortality for HIV +ve pts admitted to ICU for neuro reasons. 3. GI. Bleeding HIV related (Kaposi's, lymphoma) or non related (ulcers, varices). May be exac by HIV-associated thrombocytopenia. Bowel perf (CMV enteritis, Kaposi's, lymphoma). Pancreatitis. 4. CV - IHD related to HAART 5. Sepsis of other origin 6. Unrelated admission Immune reconstitution inflammatory syndrome (IRIS). Paradoxical worsening of infectious processes on commencement of ART. Usually self-limiting but may warrant delay in initiation if pt has a neuro OI. Steroids controversial.

Answer 151

Direct thrombin inhibitors - Dabigatran - (Argatroban and bivalirudin considered separately - used in HIT) Factor Xa inhibitors (all have an 'Xa' in them) - Apixaban, rivaroxaban, edoxaban - (Fondaparinux considered separately - NSTEMI/unstable angina/VTE) All 4 NOACs are licensed for stroke prevention in AF, and VTE treatment/secondary prevention. All except edoxaban are licensed for VTE prophylaxis post elective TKR/THR. Rivaroxaban is now also licensed for ACS. Pros of NOACs Quick onset, short half lives, similar or better efficacy, fewer drug interactions, no monitoring requirement, fixed dose guidelines Cons Only dabigatran has an antidote, limited experience, affected by renal impairment, no widely available measure of activity. Dabigatran causes dyspepsia. ``` Trials for AF anticoagulation - RE-LY: dabigatran - ROCKET-AF: rivaroxaban - ARISTOTLE: apixaban All superior to warfarin and bleeding outcomes same or better. Meta-analysis of the 3 agents did not come up with anything significant to differentiate them. Apixaban may be better in renal impairment. ``` Surgery Withold and wait 1-2 elimination half lives ideally Bridging decided on individual basis MDT approach with haem General haemostatic measures intra/postop ``` Bleeding Withold drug, general resuscitation measures Tranexamic acid Consider FFP Consider plts if <70 Consider PCC Consider activated charcoal if <2h CVVHF or idarucizumab for dabigatran (ongoing phase 3 RE-VERSE AD study; £2.4k per dose) Not factor 7 - arterial thrombosis ```

Answer 152

Afferent limb: identification of pt deterioration using track and trigger systems Efferent limb: response to pt deterioration - Ramp-down or ramp-up systems (initial vs eventual involvement of specialised critical care staff; latter more common in UK) - Evidence for MET teams improving outcomes - MERIT (Aus), Priestly (UK) Administrative limb Governance limb

Answer 153

``` Quality indicators Early death (<4h ICU admission) Late death (>7d) OOH discharge (10pm-7am) Delayed discharge (>4h) Unit-acquired infections Standardised mortality ratio (observed/expected deaths) Readmission rate (target <1.8%) ``` Limitations of SMR - Does not account for pre or post ICU care factors - Reliant on data collection - Small units are at greater risk of error and variation from the norm - Death not necessarily most important factor - Case mix and illness severity must be taken into account ICNARC Ongoing Case Mix Programme and database Outcome data Resource allocation Outcomes - ICU mortality (simple but variable definition of 'ICU' between hospitals; can be 'gamed' e.g. by transfers out to die) - Hospital mortality (avoids ICU definition problems but blurs ward care problems with ICU) - 90 day mortality (includes post discharge mortality but is an arbitrary time point and loss to follow up is a problem) - 1 year functional outcome (is a ‘POEM’ - patient oriented endpoint that matters; considers disability and LT consequences of critical illness, but no ideal scoring tool available, and all are time consuming/labour intensive/costly and suffer loss to follow up)

Answer 154

Principles Transfer entails risk Avoid if possible Maintain standard of care during (personnel, monitoring, therapy where possible) Prehospital/intra-hospital/intra-unit/inter-hospital Clinical (diagnostic/therapeutic/specialist care)/non-clinical Proven risks: VAP, PTX, atelectasis, glycaemic problems, hypernatraemia, increased LoS. No mortality difference in study of 3000 transfers in France. Factors Risk/benefit ratio Urgency/time critical? Physiological stability Expected trajectory (e.g. need for I+V prior to transfer) Duration of transfer (to calculate consumables) Access to pt during transfer (e.g. air transfer) Preparation Patient, personnel, equipment and drugs 1. Stabilise patient 2. Prepare for transfer Considerations Pt often required to lie flat for prolonged period Suboptimal ventilator Altitude considerations - lower pO2, expansion of PTX Good IV access - min 2; art/NG/catheter Notes and scans Communication with receiving unit, pt and family Establish on transfer equipment and reassess stability Level 1 - paramedic + nurse Level 2 - medical escort if deterioration/intervention anticipated Level 3 - nurse + airway trained doctor Vent/BVM/airway equipment/O2 Ongoing drugs/emergency drugs Charged equipment ``` Road - cheap, widely available, less prone to weather disturbance; longer duration, cannot reach some areas Fixed wing (for >150miles) - speed; high altitude problems, noisy, cramped, cost, training, still need road transfer between airport and hospital Helicopter - speed, scene access and direct hospital access if helipad, lower altitude; noisy, limited pt access, cost, training, slower than fixed wing ``` Altitude Low PiO2 Expansion of gas-filled cavities (PTX, ETT cuff, gut, pneumocephalus/peritoneum/mediastinum etc)

Answer 155

Higher morbidity and mortality, duration of MV, LoS Associated comorbidities Manual handling and equipment issues Difficult airway and challenging perc trache Reduced FRC, shorter time to apnoeic desat Less compliant chest wall and high pleural pressures Calculation of Vt on IBW Difficult vascular access and NIBP Higher protein intake needed Increased Vd of fat-soluble drugs; normograms may not apply; do drug levels Some drugs IBW, some TBW

Answer 156

Up to half of survivors Cognitive, psychological and physical aspects Impact on family Cognitive: memory difficulties, reduced attention span, impaired executive function RFs: previous cognitive impairment, ARDS, sepsis, delirium Psychological: PTSD, anxiety, depression RFs: above + hx psych illness, female, <50, low educational level, prolonged sedation or BDZ Physical: respiratory, MSK RFs: prolonged MV, MOF, sepsis, prolonged bed rest, hyperglycaemia Interventions on ICU Minimise sedation, early mobilisation, avoid RFs, therapy input, early rehab plan, family involvement, patient diary Interventions post ICU Follow-up clinics, to include assessment for common rehab issues

Answer 157

Patient's known wishes/family views LPA/AD Comorbidities Functional status Current illness - reversibility, likelihood of survival and likely dependence thereafter Trajectory of impairment over preceding months Resus status Aim of ICU admission - restorative to previous or lower level of function; palliative

Answer 158

``` Laparotomy for peritonitis Bowel resection Therapeutic OGD Peptic ulcer surgery Gastrectomy Splenectomy ``` Other high risk groups - Dialysis-dependent - Immunosuppressed - Long term steroids - Long term beta blockers - High ASA - Massive transfusion - Lactate >4 or significant organ dysfunction postop

Answer 159

Bleeding - 400ml first hour/200ml/h 2h/100ml/h 4h acceptable - Beware tamponade - Medical - residual heparin, thrombocytopenia/plt dysfunction, consumption of clotting factors - Surgical - failed haemostasis Myocardial dysfunction - Arrhythmias (1/3 get AF; bradyarrhythmias in valve replacements as near AVN) - Impaired systolic and diastolic function - On a background of established disease - Proportionate to duration of CPB - Reduced by cardioplegia (esp hyperosmolar), hypothermia - Usually due to ischaemia-reperfusion injury but can also be kinking/spasm/air embolism to vessels - Pericarditis can occur Hypothermia - Acidosis, coagulopathy - Vasoconstriction raises AVR - Shivering increases O2 demand Others - ARDS - Atelectasis - AKI - Delirium - Stroke

Answer 160

Thoracic AA - Variable surgical approach - May need CPB/DHCA/selective or retrograde cerebral perfusion - Comps: spinal cord ischaemia (keep spinal cord perfusion pressure>80 (MAP-CSFP) and serial neuro ex), AKI, bleeding/coagulopathy, MI/stroke AAA - 6% mortality elective repair - Hardman index for emergency repair - Comps: ischaemia-reperfusion with MOF, AKI, ischaemia distal to XC, MI, embolism, bleeding/coagulopathy, abdo compartment syn (may need laparostomy) EVAR - Risks: conversion, endoleak, bleeding/coagulopathy, stroke, limb ischaemia, spinal cord ischaemia, rupture, dissection, AKI, post-implantation syndrome (SIRS in absence of infection - treat with NSAIDs)

Answer 161

``` Complications Bleeding, haematoma Cerebral ischaemia Raised ICP Seizures Cerebral oedema Pneumocephalus with potential for tensioning CSF leak with potential for infection Neurogenic pulmonary oedema DI and endocrine disturbance ``` Beta blockers are first line in hypertension as they do not directly affect ICP Negative fluid balance is associated with worse outcomes in TBI No difference in outcomes post TBI with ICP targeted therapy vs regular imaging directed therapy

Answer 162

A vascularised area of tissue and its neurovascular bundle are removed from a donor site and transferred to a new region with microvascular anastomosis. Used in delayed reconstruction post cancer surgery, trauma, burns. Flap failure causes - Thrombosis - Ischaemia-reperfusion (hypotension, vasoconstriction) - Flap oedema Flap monitoring Colour, temperature, cap refill, texture US Doppler Optimisation of O2 delivery - Oxygenation - Normothermia and core-peripheral gradient <1C - BP control - Extreme caution with vasoconstrictors - Hct target 30% - Smooth extubation to avoid BP surges

Answer 163

Bronchial ca > trauma > massive haemoptysis 11% 30 day mortality (higher with R than L, ?why). Mortality higher if emergency op. Immediate anatomical changes - Post-pneumonectomy space (PPS) fills with air (drains are not routine) Late anatomical changes - Raised hemidiaphragm - Mediastinal shift towards PPS - Remaining lung hyper-inflates - Complete opacification of hemithorax on CXR by 4/12 Lung vols, FVC and DLCO all reduce but by less than 50%. Complications - Pulmonary oedema of remaining lung due to increased hydrostatic pressure (high mortality) - Haemothorax (suspect if the PPS is filling up within 24h postop) - need return to theatre - Chylothorax - within 3/52 postop - BPF (suspect if fluid level drops after rising) - Post-pneumonectomy syndrome * SOB, stridor, recurrent infection * Caused by compression of trachea and remaining mainstem bronchus by post-resection mediastinal shift * Needs operative intervention - Others: empyema in PPS, contralateral PTX, arrhythmia, MI, AKI, scoliosis, cardiac herniation (movement of heart into PPS through pericardial defect - can lead to twisting of great vessels with subsequent collapse), spinal cord ischaemia and paralysis Risk of comps higher in elderly, obese, COPD, comorbidities, current smoker Important stuff Analgesia, early extubation, physio, vigilance for comps Restrictive fluid strategy/guided fluids to avoid pul oedema of remaining lung

Answer 164

Infection of the endocardial surface of the heart Sterile plt-thrombin vegetation gets haematogenously seeded M:F 3:1, mean age 60 Mortality overall 15% Fever, new murmur, haematuria, peripheral stigmata, features of embolic stroke. Subacute can be v vague/non-specific. Duke criteria Classification - Clinical - acute/subacute - By location/nidus of infection - native, prosthetic (early/late), device-related, right-sided. Also sterile (Libman-Sacks) RFs: previous endocarditis, structural heart disease (congenital, acquired, degenerative), IVDU, immunosuppression, bacteraemia, DM, prosthesis/device, postop haematoma from device insertion, preceding TPW Orgs: 70% viridans group streptococci, enterococci, staph. IVDUs more likely to have staph, strep, Gram negs or polymicrobial, fungal. Prosthetic early (staph aureus, coagulase nega staph). Prosthetic late same as native. Comps: valvular destruction, arrhythmia, cardiac failure, abscess, MI, pericarditis, arterial emboli, stroke, brain abscess, glomerulonephritis

Answer 165

An increase of SV of 10-15% after a 500ml crystalloid fluid challenge over 10-15m. Increased SV indicates increased CO which indicates increased O2 delivery. Implies that pt is on the ascending portion of the Starling curve (they have 'preload reserve'). Static markers - HR, BP, cap refill, UO, collapsed veins - CVP/PCWP - CXR - EVLW/ITBV - Lactate and SvO2 (as single measurements) Dynamic markers - Passive leg raise - PPV/SVV - 15s end-expiratory occlusion test (acts like a fluid challenge) - monitor CI/PPV - Ultrasound of lung or IVC - Echo (EDV, velocity time index)

Answer 166

Reduced CMRO2 - GA/sedation - TBI High flow states: sepsis, hyperthyroidism, severe liver disease

Answer 167

An inflammation of the peritoneum caused by pathogenic microorganisms and their products. Can be localised or diffuse.

Answer 168

Colloid solution - 4, 10, 20% Prepared from pooled human plasma Use in the critically unwell is controversial - conflicting evidence. May be beneficial in ARDS (with furosemide) to increase oncotic pressure. May be harmful in TBI/trauma. Indications - Volume replacement - Hypoalbuminaemia esp SBP Risks: infection, allergic rxn, cost Ascites >5L: 100ml 20% HAS for every 3L

Answer 169

Respiratory impairment from submersion/immersion in liquid. Causes: misadventure/impaired judgement, inadequate supervision of children, medical episode (neuro/cardiac), trauma, overdose, foul play Issues - lung insult (osmotic then potentially infective) - brain insult (hypoxic-ischaemic) - hypothermia - underlying cause - trauma, medical etc Comps - MODS - ARDS - Neg press pul oedema - Electrolyte disturbance ``` Events Water spat/swallowed Eventually enters mouth Breath holding for about 1m Inspiratory drive irresistible Water aspirated Reflex coughing +/- laryngospasm Continued aspiration Hypoxaemia LOC and apnoea Final mode of death is cardiac dysrhythmia: tachy --> brady --> PEA --> asystole Whole process seconds to minutes ``` Survivors have brain injury proportionate to severity and duration of cerebral hypoxia ``` Lung injury Surfactant washout Osmotic gradient disrupts alveolar basement membrane Fluid and electrolyte shifts Massive bloodstained pulmonary oedema Reduced compliance V/Q mismatch Atelectasis No major diffs salt/freshwater despite electrolyte diffs ``` Infection More orgs in fresh than salt water - Gram negs, anaerobes, Staph, fungi, algae, protozoa Hypothermia Can be protective ``` Management ATLS LTVV NG and decompress stomach Rewarm to 34C for 24h Neuroprotective measures Abx if contaminated water CO monitoring ``` Poor prognostic factors Immersion >10m, delayed CPR, CPR>35m, asystole, unreactive pupils, pH<7, loss of grey-white matter differentiation on CT within 36h, GCS<5 at 24h

Answer 170

Not closed post laparotomy Primary laparostomy Treatment/strong anticipation of abdominal compartment syndrome Pros: decompresses abdomen Cons: need for second op, cannot prone pt, infection risk, psychological Risks: adhesions, lateralisation, loss of skin/fascia, ileus, nutritional problems, inability to close, fistulae ``` Mx Plan for closure immediately Negative pressure dressings Positioning Nutrition ```

Answer 171

Indications Airway management - RSI, trache Facilitation of MV (improves chest wall compliance, reduces Paw) ICP control Reduction of muscle tone - status epilepticus, tetanus, NMS Safe transfer Risks - Prolonged duration in renal failure - Inadequate sedation - PTSD - Unrecognised ventilator disconnection - Secretion retention and infection risk as cough suppressed - Delayed diagnosis of acute abdomen - Neuro exam impossible - Higher risk of VTE and pressure sores due to immobility - Infusions >24h are a/w prolonged muscle weakness - Subluxation of unstable C spine fractures Potentiation of NDMBs - Acidosis (met/res) - Low K/Ca, high Mg/Na - CCBs, BBs, LAs, aminoglycosides, immunosuppressants, H2 blockers - NM disease - MG, MD Should monitor block in pts on infusions TOF count 1-2hrly

Answer 172

Malignancy of lymphoid tissue (cf. myeloid) HL, NHL (biggest group), MM and immunoproliferative diseases B symptoms - fever, night sweats, weight loss Ann Arbor staging RFs HL - EBV, FHx NHL - HIV, HTLV, immunosuppression, smoking Haem malignancy presentations to ICU - Neutropenia and sepsis - Respiratory failure (infection, PE, pul haemorrhage from thrombocytopenia) - Tumour lysis syndrome - Haemorrhage - GvHD Need for MV/RRT poor prognostic sign Only up to 40% haem ICU pts survive to discharge

Answer 173

``` Thyroid Diabetic Sodium Adrenal Parathyroid Panhypopit - postop, Sheehan's ```

Answer 174

Tissue hypoperfusion that is primarily attributable to myocardial dysfunction. SBP<90 or MAP<30 from baseline, CI <1.8 unsupported or 2.2 supported, with adequate filling pressures. Ev of end organ hypoperfusion (brain, kidneys, peripheries) Most common cause LVF due to acute MI, STEMI>NSTEMI. Mortality 50% if successful PCI, >80% if not Ventilatory strategy - Small fluid bolus and early vasoactives beforehand - Good pre-O2/HFNC; consider DSI to facilitate - Some ev that pts on MV wean from IABP faster - Titrate PEEP to oxygenation/WoB/haemodynamics - De-escalate FiO2 post intubation - ARDSnet standard stuff Differentials: sepsis, massive PE, tamponade, PTX, severe obstructive lung disease Dobutamine +/- NA if BP drops Consider inodilators IABP

Answer 175

Presentation to ICU - Encephalopathy - Sepsis - Renal failure - Variceal bleed - Cardioresp failure Cause of acute decompensation - Sepsis inc SBP - GI bleed - Drugs (opiates, sedatives, propranolol) - Alcohol - Electrolyte disturbance - HCC - Portal vein thrombosis - Dehydration - Constipation Hx: EJAC, abdo pain/swelling, N+V, pruritis, fatigue, alcohol, drugs, travel, BBV RFs Ex: palmar erythema, bruising, spider naevi, cachexia, icterus, asterixis, gynaecomastia, hepatosplenomegaly, ascites ``` Tx Treat cause, supportive Albumin 1g/kg loading then 20-40g/day (binds inflammatory cytokines) Lactulose Glycaemic monitoring Correct coagulopathy only if bleeding; VTE prophylaxis Vasoconstrict Ascitic drainage TIPSS Transplant ``` Cirrhotics in ICU have 40-80% mortality. Ammonia correlates less well with encephalopathy in CLD. ``` Causes of ascites - portal HTN - hypoalbuminaemia - peritoneal disease Problems: pressure effects (ACS/low FRC), SBP, HRS Tx diuretics, drainage 100ml 20% HAS for every 3L ``` Indications of successful OLTx Lactate clearing Glucose rising Coag normalising Problems: primary non-function, art/ven thrombosis bile leak/obstruction, sepsis

Answer 176

3 times more common than AAA rupture Stanford/DeBakey/Svensson Blood enters media via a tear, disruption of vasa vasorum or atherosclerotic ulcer. Sudden severe pain + end organ features. RFs/causes: HTN, smoking, other CVS RFs; inherited disorders in <40s (Marfan's, EDS etc); previous cardiac surgery, recent cardiac cath, syphilis, vasculitis, pre-existing AAA, cocaine O/E hypertensive (check for discrepancy), new AR, shock, heart failure, weakness, Horner's, acute SVCO from aortic compression Comps: AR, rupture, MI, tamponade, ischaemia of anything, death Ix ECG: normal, STEMI, electrical alternans Trop CXR widened mediastinum/abnormal aortic contour TTE - good for ascending + cardiac comps TOE CT Aortography MRI/A Priorities - BP control - Bleeding control Tx: O2, big access, invasive lines, code red, correct coagulopathy, TXA, get SBP down to 100-120 with labetalol, cardiothoracic opinion Intraop - stable induction, full/fast/forward, CPB +/- DHCA (max 45m at 18C)

Answer 177

85% in bone Low <0.8 PTH increases release from bone but also renal excretion Vit D increases gut absorption Functions: ATP, cAMP, 2,3-DPG, nucleic acids, phospholipid membranes, enzyme co-factor, glycolysis, buffer, coagulation, immune Reduced intake: malnutrition, malabsorption Redistribution: refeeding syn, insulin Increased excretion: diuretics, diarrhoea, burns, phosphate binders, RRT Problems: ventilator dependence, weakness, heart failure (reversible DCM)

Answer 178

``` Identify hazards Identify persons at risk Evaluate risk Record findings Review ```

Answer 179

Indications - Analgesia - Anxiolysis - Anaesthesia for procedures/periods of neuromuscular blockade* - ETT tolerance - ICP control* - Seizure control* - Advanced ventilatory strategies* *indications for deep sedation Propofol max 4mg/kg/h Usual maintenance 0.3-3mg/kg/h Start at 0.3mg/kg/h and uptitrate every 5m until desired level of sedation achieved Midaz 0.25 - 1 μg/kg/min or 0.5-2mg IV boluses Fent 0.01-0.03 mcg/kg/min, titrated up every 15-30m, max 50-100mcg/h Dexmed - no resp depression; brady and sinus arrest can occur. MIDEX: dex>midaz for earlier liberation from vent. PRODEX: no diff. Also has anti-inflammatory properties. Load with 1mcg/kg over 10m then 0.2-0.7mcg/kg/h. Clonidine 0.5- 2mcg/kg/h Ketamine not really used for ongoing sedation due to hallucinations but used for short procedures esp paeds/burns/trauma Volatiles in ICU - Anaconda (anaesthetic conserving device) ``` CI to sed hold Prone Raised ICP Paralysed Uncomfortable mode of MV Critical device ```

Answer 180

Patient related - Airway obstruction - Obstructive airways disease; prolonged expiratory time - High secretion load - Pulmonary oedema - PTX - Pain/anxiety - Abdo distension - High respiratory drive for any reason Ventilator related - Stacking - Leak - Disconnection - Triggering problem - delayed, auto, double - Cycling problem - premature, delayed - Incorrect ventilator support - Low FiO2 - Excessive dead space - Malfunction

Answer 181

Immunological dysfunction Catabolic state Psychological disturbance

Answer 182

Duty to: - inform pt when something goes wrong - apologise - offer remedy/support - explain the implications Ensure incident form has been completed and that lessons are learnt/shared

Answer 183

* Local services should be freed from government targets, national IT systems and regulations, and allowed to design their own services and procedures. (Frontline professionals are spending over 60% of their time at computer screens). * Inspection of safeguarding services should be unnanounced, and should look at all services, including police, health and education, as well as social work. * The government should work with health professionals, such as the Royal College of Paediatrics and Child Health, to ensure that the NHS reforms do not adversely impact on effective safeguarding partnership arrangements. * Every local authority should employ a principal child and family social worker – a senior manager who is still actively involved in frontline work – to report the views of professionals to management.

Answer 184

Definition: pts on anticancer tx with neuts <0.5 and either fever >38, or other signs/sx consistent with clinically significant sepsis Fluoroquinolone prophylaxis in pts expected to have neuts<0.5 during the expected period of neutropenia only Beta lactam monotherapy is first line; no aminoglycoside unless local/pt specific indication Continue for at least 48h Do not switch abx based on continuing fever alone Multinational Association for Supportive Care in Cancer risk index - a scoring system for identifying low-risk cancer patients with febrile neutropenia.

Answer 185

Preop - Hair removal only if necessary, and clippers not razors - Antibiotic prophylaxis for prosthesis/implant/contaminated surgery; not routinely for clean, non-prosthetic, uncomplicated surgery. Give at induction, or earlier if tourniquet used Intraop - Skin prep - Dressings Postop - Tissue viability input for wounds healing by secondary intention

Answer 186

``` Ix to consider CK Urinary myoglobin IAP US/CT KUB Renal angiogram/DSA/CT/MR Functional - nuclear med (determines likelihood of recovery) ``` ``` Intrinsic renal disease Urine microscopy Vasculitis: ANCA SLE: ANA, anti-dsDNA, complement Pulmonary-renal: anti-GBM Myeloma screen HIV/HBV/HCV Renal bx (rare) ``` Creat drops in ICU pts due to disuse atrophy - poor marker UO insensitive/non-specific Novel biomarkers e.g. cystatin-c Renal functions - excretory - homeostasis - metabolism (P450) - endocrine (epo) - immune (cytokine secretion, macrophage activation)

Answer 187

Precise definition does not exist. Features: 1. Severe hypovolaemia (200ml+/kg deficit - double that of DKA) 2. Severe hyperglycaemia (30+ without significant ketonaemia (<3)) or acidosis (pH>7.3, bicarb>15) 3. Very high osmolality >320 Insidious onset over days, unlike DKA (hours) Mortality is 15-20% Tx 0.9% NaCl resuscitation (Na will initially rise; this is not an indication for hypotonic fluid) First bag over 1h, or faster if SBP<90 Aim for +ve FB of 3-6L by 12h; 50% of the fluid deficit in first 12h and the other 50% over the next 12h Monitor osmolalities as response to tx - aim 3-8 mosmol/kg/hr Do not allow >10mmol/L per 24h drop in Na FRII 0.05u/kg/h ONLY when glucose no longer falling with fluids alone, OR from the start if ketonaemia>1 (DKA/HHS overlap) Max glucose fall 5mmol/L/h If glu falls <14, start 10% dex and continue saline Biochemistry expected to normalise by 72h (target glucose 10-15) K+ replacement is same as for DKA, i.e. none>5.5, 40mmol/L between 3.5-5.5, and central replacement <3.5 Monitor GCS Treat precipitants - often sepsis Prophylactic LMWH Protect heels if obtunded Diabetic review Will prob need period of stability on insulin before going onto/back to PO hypoglycaemics, if at all ``` Comps Fluid overload Cerebral oedema Osmotic demyelination Arterial and venous thrombosis inc. MI Foot ulceration Sepsis Refeeding syndrome if previously malnourished ``` ``` Indications for critical care Osmolality >350 Na>160 pH<7.1 K<3.5/>6 GCS<12 SpO2<92% SBP<90 HR>100/<60 UO<0.5ml/kg/h Creat>200 Hypothermia Macrovascular event e.g. MI/stroke Serious comorbidity ``` Why not to give insulin too soon: risk of precipitous drop in osmolality causing cardiovascular collapse and cerebral oedema. In summary, the targets: - Glucose fall max 5mmol/L/h - Osmolality fall 3-8 mosmol/kg/h Resolution by 72h.

Answer 188

``` Neuro - SNS Catecholamines Cortisol RAAS Na/H2O retention ``` Endocrine ACTH, GH, ADH, PRL, cytokines, endorphines, acute phase reactants ``` --> catabolic state FAs mobilised AAs metabolised Hyperglycaemia Low insulin Raised BMR Negative N2 balance ```

Answer 189

Only if on >10mg pred/day, or if were on steroids within the preceding 3 months (otherwise no need to cover) Minor surgery - 25mg hydrocort at induction Moderate - usual steroid + 25mg at induction + 100mg/day for 24h Major - usual steroid + 25mg at induction + 100mg/day for 48-72h

Answer 190

Allergic Infections Neoplastic

Answer 191

Innate - Barriers - Reflexes - Complement Adaptive - Humoral (B) - Cell-mediated (T)

Answer 192

Plasma esterases - remi, sux, atracurium Kidney - midaz Lung - MAOi Gut - GTN

Answer 193

Muscle contraction Coagulation Bone and teeth structure Neurotransmitter release

Answer 194

Most prevalent neurodegenerative disorder in the elderly 1% at 65y, 15% at 85y Biggest RF age Probably environment + genetics (apolipoprotein E is major susceptibility locus) Amyloid beta plaques and neurofibrillary tangles Disorder of impaired cholinergic transmission Anaesthesia may be a RF and may be cumulative (animal study ev) EJA 2012 Sztark - RR dementia 1.35 if had anaesthesia in last 2y ``` Tx - anticholinesterases Rivastigmine, galantamine, donepezil NMDA antagonists - memantine Also symptomatic - antidepressant, anxiolytic, antipsychotic Avoid anticholinergics - atropine ```

Answer 195

Increased HR Increased O2 consumption Increased CO2 production + later rise in temp Masseter spasm Differentials: sepsis, thyroid storm, phaeo, drugs, anaphylaxis ``` Comps Hyperkalaemia Metabolic acidosis Rhabdo AKI DIC Arrhythmias ``` Avoid CCBs as interact with dantrolene - cardiac depression ``` Ryanodine receptor (chr 19) Aut dom, variable penetrance Uncontrolled Ca release from sarcoplasmic reticulum into cytoplasm of skeletal muscle ``` ``` Tx ABCDE I+V, 100% O2 Propofol TIVA, clean machine Dantrolene Cooling Invasive lines ICU Anticipate comps - serial CK MH testing ```

Answer 196

Damage to autonomic nerves - SNS/PNS or both Commonest cause DM - affects 25% T1s and 34% T2s Inherited - prophyria, amyloidosis Acquired - chronic liver disease, B12 def, alcohol, chemo, amiodarone, HIV, GBS, RA, SLE, neoplastic, tetanus Mechanisms: autoimmune, free radicals, hyperglycaemic damage Features - CVS: orthostatic hypotension, resting tachycardia (if PNS affected), fixed HR, no phase 4 overshoot on Valsalva, no sinus arrhythmia, silent ischaemia, long QT - GI: gastroparesis - GU: atonic bladder - Other: sweating (gustatory/nocturnal/absent), sexual dysfunction, dependent oedema, large pupils with delayed light response Tests SNS: postural drop >30mmHg PNS: Valsalva, R-R interval AN manifests in larger nerves first; (vagus accounts for 75% of PNS activity) - hence PNS sx predominate. Problems Big BP drop on induction (and neuraxial) Compounded by lack of pressor response PPV drops CO Exaggerated hypothermia - no vasoconstriction Clinical parameters useless for depth of GA High risk silent MI

Answer 197

Problems highlighted: Poor ax, planning and judgement AFOI indicated but not used SADs used inappropriately Cannula cric has 60% failure rate A third of events occurred during emergence - mostly obstruction A quarter of events were from ED (relating to RSI) or ICU (displaced trache) and had worse outcomes Aspiration single largest cause of death in airway disasters Failure to use capnography contributed to 70% of deaths Common pt themes Obesity Head and neck cases Recommendations Anaesthetists should train in surgical cric Capnography in all airway intervention

Answer 198

Permanent injury in 2-4 in 100,000 (pessimistic) Mainly epidurals, but CSEs over-represented Mostly for perioperative analgesia Failure to detect or understand relevance of leg weakness a big factor Organisational deficiencies a problem

Answer 199

1 in 19,000 overall 1 in 8000 with MRs, 1 in 136,000 without 1 in 670 GA sections Two thirds during induction or emergence RFs Thio, TIVA, MRs, female, middle age, OOH, junior anaesthetist, cardiac, obstetric, trauma, neuro, emergency, previous awareness, obesity, difficult airway 41% have at least moderate psychological sequalae BIS only used in 3% ``` Recommendations Nerve stim essential with MRs TIVA and depth of anaesthesia training Warn patients Surgeon to ask if they can start ```

Answer 200

Neuronal - baroreceptors, reservoirs constricted Hormonal - ANP down, ADH up, RAAS Haem - dilution, epo

Answer 201

Alpha then beta Preop - no ST/T changes on 5m ECG, nasal stuffiness, post drop, BP<140/90 Urinary catecholamines/metanephrines MRI Headache, palps, sweating Avoid histamine releasing drugs Steroid replacement Vigilance for hypoglycaemia

Answer 202

``` Hypo Pseudo - chol, glu Hypo - renal, GI, burns, trauma, pancreatitis Eu - SIADH, hypotonic fluids Hyper - CLD, CCF ``` Hyper Hypo - diuretics, burns, GI Eu - DI (or hypo) Hyper - Cushing's, Conn's, hypertonic saline, bicarb

Answer 203

``` Hypo Pseudo - drip arm Reduced intake - alcoholics Redistribution - insulin, refeeding Increased output - GI, RTA ``` Hyper Increased intake - fluids Redistribution - rhabdo, dig, sux Decreased output - CKD, K sparing diuretics

Answer 204

``` Drugs Beta agonists Mag Adrenaline Steroids Ketamine Sevo ``` Ventilation of the asthmatic (LITFL). Hypotension post induction: stacking, hypovolaemia, induction drugs, tension PTX (SHIT). - No clear benefit of one mode over another - Tidal volume 6-8 mL/kg - Slow respiratory rate (e.g 8-10/min) - High inspiratory flow rate (e.g 80-100L/min) to allow longer expiratory times - PEEP of 0 - FiO2 titrated to keep SaO2 >93% Expect the following with these initial settings in a patient with asthma: - high peak inspiratory pressures (PIP) — don’t worry, this does not necessarily correlate with lung barotrauma - respiratory acidosis due to a low target minute ventilation — sedation and neuromuscular blockade may be required to suppress spontaneous ventilation ``` RFs for death Previous life-threatening asthma with acidosis or need for ventilation Hospital adm in last yr 3 or more meds Heavy beta agonist use Brittle asthma Adverse psycho-social circumstances ```

Answer 205

- Wellens’ syndrome - biphasic OR deeply inverted T waves in V2/V3 (+/- I and aVL) - indicates critical LAD stenosis (T waves go up then down - opposite of hypokalaemia, in which they go down then up) - de Winter’s T waves - LAD occlusion (downsloping ST depression then a tall, peaked ‘rocket' T wave) - ST elevation in aVR>1mm with ST depression elsewhere - LMS occlusion (70% mortality untreated); can also be seen in severe 3VD, severe anaemia/hypoxaemia, and post ROSC; similar pattern can also be seen as rate-related change in SVT - Posterior MI - horizontal ST depression V1-3, often with ‘upright' T waves; ST elevation seen in posterior leads (V7-9; only need 0.5mm to diagnose) - RV infarction - ST elevation V1/V2, probably with inferior changes (RCA occlusion)

Answer 206

Sustained inflation: 40s of 40 cmH2O Sigh breaths: large Vt or high Pinsp for 1 or more breaths Extended sigh: increase PEEP with same driving pressure over 2m Incremental ramping of PEEP every 2 min PCV with PEEP 25-30 and PIP 40-45 for 2 min then gradual step down

Answer 207

Vitamins B1, B2, B6, vitamin C, nicotinamide and glucose.

Answer 208

Gut, skin, liver Donor T cells are the cause Steroids first line tx, effective in 50% Second line extracorporeal photophoresis, IL2 abs, cyclosporin/tac, infliximab/etanercept, sirolimus, MMF If transfusion-associated, 100% mortality

Answer 209

Treat high Mg with Ca SSRI OD - BDZ CCB/BB OD - insulin (HIET - hyperinsulinaemia and euglycaemia) HD for BLAST and vanc, gent, carbamazepine, valproate, metformin, methotrexate Ethylene glycol (cerebral oedema) - ethanol/fomepizole Digoxin - phenytoin, Digibind TCA - bicarb, possibly Intralipid Mechanism of bicarb in TCA OD: plasma alkalinization causes increased drug plasma protein binding (hence can also hyperventilate if I+V), intracellular hypopolarisation, sodium load High anion gap - ketones, alcohols, paraldehyde, aspirin, cyanide, iron, isoniazid Normal anion gap - either GI or renal losses PRIS causes Brugada like ECG and bradyarrhythmias Drug sources of lactate: metformin, LT linezolid, reverse transcriptase inhibitors, salbutamol, Hartmann's, RRT lactate buffered solutions Methanol - eye signs - dilated pupils, papilloedema, disc hyperaemia. Metab to formic acid. 10ml blindness, 30ml fatal. Paraquat - farmers, pharyngeal ulceration, renal and respiratory involvement. Avoid excess FiO2. Sodium dithionite added to urine turns it blue if paraquat present. Paraquat assay can also be done on plasma. LA toxicity: Intralipid 20%, 1.5ml/kg over 1 min then 0.25ml/kg/min for 30-60 mins E.g. 70kg man - 100ml bolus, then 600ml over 30 min. Can repeat bolus 1 or 2x for asystole, at 5 minute intervals. Dantrolene - 2-3mg/kg up to max 10mg/kg until HR/temp/EtCO2 begin to reduce. Can cause hypokalaemia but avoid replacing K+ as this can re-trigger MH.

Answer 210

Acid test Is the person subject to continuous supervision and control? Is the person free to leave? Does not apply to life-saving tx as pts are not in state detention - it is their illness/injury keeping them there.

Answer 211

- Might improve acidosis, but the latter can be an adaptive response (increases O2 release to tissues via right shift) so opposing it makes no physiological sense (although it may make numbers better) - Is a significant CO2 load which can in fact worsen acidosis (and frustrate MV weaning) - Big sodium load - Can delay fall in lactate and ketones in DKA and may contribute to cerebral oedema

Answer 212

``` Barotrauma Volutrauma Biotrauma (inflammatory cascade) Atelectotrauma O2 toxicity 21-fold increased risk of pneumonia (haematogenous/micro-aspiration/colonisation of tube - biofilm) ```

Answer 213

Immediate • Hypoxia, hypercarbia • Loss of airway • Aspiration of gastric contents • Haemorrhage (ranging from minor oozing to life-threatening arterial haemorrhage) • Damage to local structures (pneumothorax, surgical emphysema, cricoid cartilage injury, posterior tracheal wall injury, tracheal ring fracture) • Anaesthesia-related (hypotension, anaphylaxis) Early • Infection of stoma • Displacement of tracheostomy tube with loss of airway • Occlusion of tracheostomy tube • Tracheal injury (ulceration, fistula formation) • Haemorrhage (from mucosal injury or erosion into right brachiocephalic artery) Late Tracheal stenosis, dilatation, tracheomalacia

Answer 214

Venous O2 sats - ScvO2/SvO2 Arterial lactate Difference between arterial and mixed venous pCO2

Answer 215

Pharynx - ligament of Treitz 80% non-variceal, mainly peptic ulcers 10-20% mortality 15% with haematochezia have an upper GI source ``` Tx ABCDE Good access, send bloods Consider code red Correct coagulopathy Transfusion Risk stratification - Glasgow-Blatchford for OGD timing, Rockall for mortality Endotherapy for ulcers - 2 of the 3 to minimise rebleed - submucosal adrenaline - aluminium clips - bipolar diathermy (+/- haemostatic spray) Rescue - repeat OGD, angio/IR, surgery Varices - banding, sclerotherapy; rescue SBT/Minnesota, Danis stent, TIPSS/OLTx PPI if ulcer (raising gastric pH is said to prevent clot auto-digestion) Terli (0.5-2mg 4hly) and abx if varices ``` Stress ulcers - due to reduced splanchnic blood flow and loss of mucosal protective measures. RFs: increasing duration of MV, coagulopathy, MOF, AKI, previous bleed, steroids, major trauma, burns. Previously 25% pts, now 1-4%. PPI superior but may increase C.diff/VAP.

Answer 216

``` Refractory ascites Refractory variceal haemorrhage Hepatorenal syndrome Hepatopulmonary syndrome Hepatic hydrothorax (tx is diuretics, not drainage) ``` Workup for TIPSS Doppler portal vein and biliary system Echo for RV as will cause increased R heart preload; and PHTN/CCF/TR are CIs EEG as TIPSS will cause/worsen HE Procedure: Access RIJ --> VC --> hepatic vein --> portal vein Balloon dilatation of tract Stent deployed Complications can be related to access, stent or resultant shunt

Answer 217

3 or more watery stools/day (WHO) - osmotic - malabsorption, lactulose; stops with starvation - secretory - increased secretion/reduced absorption; high volume; does not stop with starvation; can be infective e.g. cholera - inflammatory - bloody; may be infection e.g. E.coli 0157, Shigella; or IBD - dysmotility (ileus, pseudo-obstruction) C.diff Gram negative bacterium 3% general pop carrier rate, 20% pts on abx Profuse watery diarrhoea, abdo pain Fever is marker of severity RFs abx esp penicillins, cephalosporins, fluoroquinolones; chronic bowel disease; recent GI surgery; PPI; immunosuppression Diagnosis: PCR indicates colonisation. CDT indicates active infection. Pseudomembranes may be seen at colonoscopy. Comps: - fulminant colitis in 3% (30-80% mortality) - toxic megacolon (>7cm) - bowel perforation Rx metro PO/IV; vanc PO only; fidaxomicin; faecal tx; surgical mx of comps ``` Other infective causes of diarrhoea Bacterial - E.coli, Campylobacter Viral - noro/rota/adeno/CMV Parasitic - Giardia, cryptosporidium May notifiable, consider HIV testing ``` Non-infective Abx - kill gut bacteria so increasing luminal carb content and causing osmotic diarrhoea Enteral feed

Answer 218

Consciousness = wakefulness + awareness together - Coma = neither awake nor aware - Vegetative state = awake but not aware (cortical damage, brainstem preserved); persistent = >4/52 - Minimally conscious state = minimal, fluctuating awareness (global neuronal damage) - Locked-in syndrome (bilateral pontine lesions) - Akinetic mutism (bilateral frontal lobe/3rd ventricle pathology) - Catatonia (psychiatric)

Answer 219

Differentials - Alcohol - Mannitol - Cold diuresis - Hyperglycaemia - DI - CSW (inappropriate release of natriuretic peptide)

Answer 220

Intracranial - CNS infection - SOL - Haemorrhage - Embolism Systemic - Drug toxicity e.g. TCA - Alcohol withdrawal - Hypoglycaemia - Hyponatraemia - Hypoxia Once pt seizure-free for 24h and loaded with an anticonvulsant, wean sedatives; failure to wake appropriately --> EEG for non-convulsive status.

Answer 221

85% ischaemic; mainly thromboembolic, also cardiac origin, SVD, vasculitis, dissection Sudden onset focal neurology Altered GCS or HA indicates raised ICP and increases likelihood of haemorrhagic pathology Exclude hypoglycaemia Neuroimaging Thrombolysis within 4.5h Direct intra-arterial thrombolysis within 6h is first line for acute basilar stroke Start aspirin as soon as bleed excluded if not thrombolysing, or after the 24h re-scan if thrombolysing (to check no bleed first); 2/52 Decompressive crani considered in <60s with large infarcts (malignant MCA) CIs to thrombolysis - haemorrhage - severe HTN - recent surgery/trauma - coagulopathy, INR>1.7 - intracranial neoplasm Malignant MCA syndrome - MCA territory stroke of >50% on CT - Perfusion deficit of >66% on CT - Infarct volume >82 mL within 6h or >145ml within 14h on MRI Trials: DESTINY 1/2, DECIMAL, HAMLET Age <60 - reduced mortality with hemicraniectomy <48h of onset Postop severe disability very common in <60s but universal in >60s ICH: 30-50% 6/12 mortality, <20% independent. Worse outcomes in old age, larger bleed, coma on presentation, intraventricular extension, need for ventilation, post fossa bleed.

Answer 222

Clinically detectable weakness in patients in whom there is no plausible aetiology other than critical illness. It is generalised, symmetrical, flaccid and spares the cranial nerves. 50% have sensory involvement. MRC mean score is <4 in all muscle groups on two occasions over 24h apart. Divisible into myopathy, polyneuropathy and neuromyopathy. 25-80% of ICU pts ? microcirculatory damage + direct neurotoxicity + cytokine-mediated injury RFs: sepsis, steroids, NMBAs, hyperglycaemia, immobility, electrolyte derangement Ix Neuroimaging and EMG to exclude other causes (reduced action potential with normal velocity) Muscle bx reduced actin/myosin ratio Functional recovery in 70% Prevention Address RFs, physio, nutrition

Answer 223

SDD - enteral abx - gel to oropharynx and down NG; tobramycin, polymixin E and amphotericin B - parenteral abx - 4 days of anti-pseud; cephalosporin - strict hygiene - surveillance cultures SOD - just topical abx to oropharynx + chlorhex gel Both reduce RTI, bacteraemia and mortality Low uptake - antimicrobial resistance potential - ?external validity of research - resource intense

Answer 224

SS - *increased serotonergic activity* - altered mentation, neuromuscular hyper-reactivity, autonomic dysfunction - dose dependent/type A - hyperreflexia - normal WBC, CK - rapid resolution - low mortality <1% - rx BDZ, cyproheptadine NMS - *reduced dopaminergic activity* - fever, rigidity, autonomic dysfunction - dose independent/type B - idiosyncratic - hyporeflexia - high WBC, CK - slow resolution - high mortality 10% - rx bromocriptine, dantrolene

Answer 225

``` Inclusion Cardiac arrest with ROSC CPR within 15m Max 1h to ROSC Comatose Ventilated SBP>90 (with or without inotropes) ``` ``` Exclusion - absolute Primary neurological event Not an ICU candidate Temp <30 Active bleeding ``` Exclusion - relative Coagulopathy Sepsis Prolonged hypotension/hypoxia

Answer 226

Simple 60% (1 SBT) Difficult 30% (7d/3 SBTs) Prolonged 6-15% (exceeding the above) Long term wean (>6h/day for >21d)

Answer 227

COPD indication: pH<7.35 + PaCO2>6.5 + RR>23 persisting after medical mx Neuromuscular indications: pH and PaCO2 as above, OR resp illness with RR>20 if usual VC<1L, regardless of PaCO2 Obesity indications: as per COPD indication, OR daytime PaCO2>6.5 and somnolent CI: abs (facial deformity/burns, upper airway obstruction), rel (pH<7.15, GCS<8, confusion/agitation/cog imp) Initial settings COPD/OHS: 15/3 (20/3 if pH<7.25). Can uptitrate over 10-30m to max 30/8 - titrate to augment chest movement and slow the RR Initial settings NM: 10/3 (or IPAP 5 above usual setting) Backup rate 16-20 I:E in COPD: 1:2 to 1:3 I:E in NM/OHS: 1:1 iTime COPD: 0.8-1.2s iTime NM/OHS: 1.2-1.5s (EPAP>8 may be needed in severe OHS/BMI>35, to recruit, to overcome PEEPi, or if v high IPAP) Keep on as much as possible first 24h Taper depending on tolerance and gases over next 48-72h Aim SpO2 88-92% all pts ``` Red flags pH<7.25 on optimal settings High FiO2 req/rapid desat off NIV RR>25 persisting New onset confusion/distress ``` --> check synchronisation, mask fit, exhalation port; consider bronchodilators, physio, anxiolytic; consider IMV