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C

CABG, see Coronary artery bypass graft

Cachectin, see Cytokines

Cachexia, see Malnutrition

Caesarean section (CS). Operative delivery of a fetus by surgical incision through the abdominal wall and uterus. Unless specifically indicated, the classical midline upper uterine segment approach has been largely replaced by the transverse lower segment incision; the latter is associated with lower rates of ileus, infection and bleeding. The CS rate in the UK has steadily increased to ~25%, from ~8–10% in the 1980s.

• Indications include: previous CS; pre-existing maternal morbidity (e.g. cardiac disease); complications of pregnancy (e.g. pre-eclampsia); obstetric disorders (e.g. placenta praevia); fetal compromise; failure to progress.

• Specific anaesthetic considerations:

ent physiological changes of pregnancy.

ent difficult tracheal intubation and aspiration of gastric contents associated with general anaesthesia (GA) have been major anaesthetic causes of maternal mortality. Mortality is higher for emergency CS than for elective CS.

ent aortocaval compression must be minimised by avoiding the supine position at all times.

ent uterine tone is decreased by volatile anaesthetic agents; however, consideration of this should not result in the administration of inadequate anaesthesia.

ent placental perfusion may be reduced by severe and/or prolonged hypotension and/or reduction in cardiac output.

ent contraction of the uterus upon delivery results in autotransfusion of about 500 ml blood, helping to offset the average blood loss of 500–1500 ml (GA) or 300–700 ml (regional anaesthesia).

ent neonatal depression should be avoided, but maternal awareness may occur if depth of anaesthesia is inadequate.

• The usual preoperative assessment should be made, with particular attention to:

ent the indication for CS (e.g. pre-eclampsia) and other obstetric or medical conditions.

ent whether CS is elective or emergency, and whether the fetus is compromised.

ent assessment of the airway.

ent maternal preference for general or regional anaesthesia.

ent if used in labour, the quality of existing epidural analgesia should be assessed.

ent assessment of the lumbar spine and any contraindications to regional anaesthesia.

The above points inform the decision to employ general or regional anaesthesia.

• Regimens used to reduce the risk of aspiration pneumonitis:

ent fasting during labour: this practice has been questioned, and many centres allow clear fluids or certain foods (low fat and sugar content) for low-risk women in labour (if not receiving opioids), although this is still controversial.

ent antacid therapy: 0.3 M sodium citrate (30 ml) directly neutralises gastric acidity; it has a short duration of action and should be given immediately before induction of anaesthesia.

ent H₂ receptor antagonists: different regimens are employed in different units, with most reserving prophylaxis, e.g. with ranitidine, for women at risk of operative intervention or receiving pethidine (causing reduced gastric emptying). For elective CS, ranitidine 150 mg orally the night before and 2 h before surgery is often given. For emergency CS, ranitidine 50 mg iv may be given; cimetidine 200 mg im is an alternative as it has a more rapid onset than ranitidine.

ent omeprazole and metoclopramide have also been used, to reduce gastric acidity and increase gastric emptying, respectively.

Sedative premedication is usually avoided because of the risk of neonatal respiratory depression and difficulties over timing.

• Anaesthetic techniques:

ent for all types of anaesthesia:

– wide-bore iv access (16G or larger).

– cross-matched blood available within 30 min.

– routine monitoring and skilled anaesthetic assistance, with all necessary equipment and resuscitative drugs available and checked.

– aortocaval compression is reduced by positioning the patient laterally during transport to theatre and surgery.

– ergometrine has been superseded by oxytocin as the first-line uterotonic following delivery because of the former’s side effects (e.g. hypertension and vomiting).

ent general anaesthesia:

– rapid sequence induction with an adequate dose of anaesthetic agent is required to prevent awareness; a ‘maximal allowed dose’ based on weight may be insufficient. Neonatal depression due to iv induction agents is minimal. Suxamethonium is still considered the neuromuscular blocking drug of choice by most authorities, although rocuronium (especially with the advent of sugammadex) is an alternative.

– difficult and failed intubation (the latter ~1 : 300–500) is more likely in obstetric patients than in the general population. Contributory factors include a full set of teeth, increased fat deposition, enlarged breasts and the hand applying cricoid pressure hindering insertion of the laryngoscope blade into the mouth. Laryngeal oedema may be present in pre-eclampsia. Apnoea rapidly results in hypoxaemia because of reduced FRC and increased O₂ demand.

– IPPV with 50% O₂ in N₂O is commonly recommended until delivery; however, in the absence of fetal distress, 33% O₂ is associated with similar neonatal outcomes.

– 0.5–0.6 MAC of volatile agents (with 50% N₂O) reduces the incidence of awareness to 1% without increasing uterine atony and bleeding, or neonatal depression; however, at 0.8–1.0 MAC, awareness falls to 0.2% and the uterus remains responsive to uterotonics. Placental blood flow is thought to be maintained by vasodilatation caused by the volatile agents, and high levels of vasoconstricting catecholamines associated with awareness are avoided. Delivery of higher concentrations of volatile agents (‘overpressure’) in 66% N₂O has been suggested for the first 3–5 min whilst alveolar concentrations are low, to reduce awareness. Factors increasing the likelihood of awareness include lack of premedication, reduced concentrations of N₂O and volatile agents, and withholding opioid analgesic drugs until delivery. Up to 26% awareness was reported in early studies using 50% N₂O and no volatile anaesthetic agent.

– normocapnia (4 kPa/30 mmHg in pregnancy) is considered ideal; excessive hyperventilation may be associated with fetal hypoxaemia and acidosis due to placental vasoconstriction, impairment of O₂ transfer associated with low PCO₂, and reduced venous return caused by excessive IPPV.

– all neuromuscular blocking drugs cross the placenta to a very small extent. Shorter-acting drugs (e.g. vecuronium and atracurium), are usually employed, since postoperative residual paralysis associated with longer-lasting drugs has been a significant factor in some maternal deaths.

– opioid analgesic drugs are withheld until delivery of the infant, to avoid neonatal respiratory depression.

– aspiration may also occur during recovery from anaesthesia (when the effect of sodium citrate may have worn off). Routine gastric aspiration during anaesthesia has been suggested, especially in emergency cases. Before tracheal extubation, the patient should be awake and on her side.

– advantages: usually quicker to perform in emergencies. May be used when regional techniques are inadequate or contraindicated, e.g. in coagulation disorders. Safer in hypovolaemia.

– disadvantages: risk of aspiration, difficult intubation, awareness and neonatal depression. Hypotension and reduced cardiac output may result from anaesthetic drugs and IPPV. Postoperative pain, drowsiness, PONV, blood loss and DVT risk all tend to be greater.

ent epidural anaesthesia (EA):

– facilities for GA should be available.

– bupivacaine 0.5% or lidocaine 2% (the latter with adrenaline 1 : 200 000) is most commonly used in the UK, often in combination. Addition of opioids (e.g. fentanyl) is common (though may not be necessary if many epidural doses have been given during labour). Bicarbonate has also been added to shorten the onset time, (e.g. 2 ml 8.4% added to 20 ml lidocaine or lidocaine/bupivacaine mixture), but risks errors from mixing up to 4–5 different drugs, especially in an emergency. Commercial premixed solutions of lidocaine/bupivacaine and adrenaline may be unsuitable as they have a low pH (3.5–5.5) and contain preservatives. Ropivacaine 0.5–0.75% or levobupivacaine 0.5% is also used. 0.75% bupivacaine is associated with a high incidence of toxicity, and has been withdrawn from obstetric use. Chloroprocaine is available in the USA and a small number of European countries (but not the UK); it has a rapid onset and offset. Etidocaine has also been used in the USA.

– L3–4 interspace is usually chosen.

– on average, 15–20 ml solution is required for adequate blockade (from S5 to T4–6). Loss of normal light touch sensation is a stronger predictor of intraoperative comfort than loss of cold sensation, although either may be used to assess the block. Smaller volumes are required for a specified level of block than in non-pregnant patients, as dilated epidural veins reduce the available volume in the epidural space.

– injection of solution in 5-ml increments at 5-min intervals reduces the risk of hypotension and extensive blockade (e.g. due to accidental spinal injection), but increases anaesthetic time and total dose. A single injection of 15–20 ml is advocated by some as producing a more rapid block. A catheter technique is used most frequently, although injection through the epidural needle may be performed.

– opioids (e.g. diamorphine 2–4 mg or fentanyl 50–100 µg) are routinely given epidurally for peri- and postoperative analgesia; maternal respiratory depression has been reported, albeit rarely.

– hypotension associated with blockade of sympathetic tone may be reduced by preloading with iv fluid; however, the use of vasopressors to prevent and treat hypotension in the euvolaemic patient is thought to be a more effective and rational approach. Ephedrine 3–6 mg or phenylephrine 50–100 µg is commonly given by intermittent bolus; continuous infusions are also effective. Phenylephrine appears to be associated with a better neonatal acid–base profile than large doses of ephedrine (thought to be due to ephedrine crossing the placenta and causing increased anaerobic glycolysis in the fetus via β-adrenergic stimulation).

– nausea and vomiting may be caused by hypotension and/or bradycardia.

– routine administration of O₂ by facemask has been questioned on the grounds of being ineffective and even possibly harmful to the fetus, due to generation of free radicals.

– during surgery many women feel pressure and movement, which may be unpleasant; all women should be warned of this possibility and of the potential requirement for general anaesthesia. Inhaled N₂O, further epidural top-ups, small doses of iv opioid drugs (e.g. fentanyl or alfentanil), iv paracetamol and ketamine may be useful. Shoulder tip pain may result from blood tracking up to the diaphragm and may be reduced by head-up tilt. Good communication between mother, anaesthetist and obstetrician is especially important when performing CS under regional anaesthesia, and the obstetrician should warn the anaesthetist before exteriorising the uterus or swabbing the paracolic gutters.

– advantages: the risks of GA are avoided. Onset of hypotension is usually slow, the mother may be able to warn of it early and it may be corrected before becoming severe. Minimal neonatal depression occurs compared with GA. The mother is not drowsy and is able to hold the baby soon after delivery. Her partner is able to be present during the procedure. Epidural analgesia provided in labour can be extended for operative delivery. The catheter can be used for further ‘top-up’ during surgery if required, and for postoperative analgesia.

– disadvantages: risk of dural tap, total spinal blockade, local anaesthetic toxicity, severe hypotension. It may be slow to achieve adequate blockade with a risk of patchy block. Inability to move the legs may be disturbing.

ent spinal anaesthesia (SA):

– general considerations as for EA.

– 0.5% bupivacaine is used in the UK; plain bupivacaine (e.g. 3 ml) produces a more variable block than hyperbaric bupivacaine (e.g. 1.8–2.8 ml), which is the only form licensed for spinal anaesthesia. Plain levobupivacaine is also licensed in the UK. Hyperbaric tetracaine (amethocaine) 0.5% (1.2–1.6 ml) is used in the USA.

– injection is usually at the L3–4/L4–5 interspace.

– advantages: as for EA, but of quicker onset. Blockade is more intense and not patchy. Smaller doses of local anaesthetic drug are used.

– disadvantages: single shot; i.e. may not last long enough if surgery is prolonged. Spinal catheter techniques allow more control over spread and duration but are technically more difficult. Risk of post-dural puncture headache (reduced to under 1% if 25–27 G pencil-point needles are used). Hypotension is of faster onset and thus may be more difficult to control; has been associated with poorer neonatal acid–base status compared with EA/GA. Remains the most popular anaesthetic technique for CS in the UK.

ent combined spinal–epidural anaesthesia (CSE):

– general considerations as for EA and SA.

– allows the fast onset and dense block of SA but with the flexibility of EA. Also allows a small subarachnoid injection to be extended by epidural injection of either saline (thought to act via a volume effect) or local anaesthetic, with greater cardiovascular stability.

– usually performed at a single vertebral interspace (needle-through-needle method)

(For contraindications and methods, see individual techniques)

CS is possible using local anaesthetic infiltration of the abdominal wall (e.g. with 0.5% lidocaine or prilocaine). Large volumes are required, with risk of toxicity. Infiltration of each layer is performed in stages. The procedure is lengthy and uncomfortable, but may be used as a last resort if other techniques are unavailable or unsuccessful. It may also be used to supplement inhalational anaesthesia following failed intubation. Transverse abdominis plane block has been used, e.g. for postoperative analgesia.

[Julius Caesar (100–44 BC), Roman Emperor; said to have been born by the abdominal route; his name allegedly derived from caedare, to cut. An alternative suggestion is related to a law enforced under the Caesars concerning abdominal section following death in late pregnancy]

Caffeine. Xanthine present in tea, coffee and certain soft drinks; the world’s most widely used psychoactive substance. Also used as an adjunct to many oral analgesic drug preparations, although not analgesic itself. Causes CNS stimulation; traditionally thought to improve performance and mood, whilst reducing fatigue. Increases cerebral vascular resistance and decreases cerebral blood flow. Half-life is about 6 h. Has been used iv and orally for treatment of post-dural puncture headache. Acts via inhibition of phosphodiesterase, increasing levels of cAMP and as an antagonist at adenosine receptors.

• Dosage: up to 30 mg in compound oral preparations. 150–300 mg orally tds/qds for post-dural puncture headache; 250 mg iv (with 250 mg sodium benzoate).

• Side effects: as for aminophylline, especially CNS and cardiac stimulation.

Caisson disease, see Decompression sickness

Calcitonin. Hormone (mw 3500) secreted from the parafollicular (C) cells of the thyroid gland. Involved in calcium homeostasis; secretion is stimulated by hypercalcaemia, catecholamines and gastrin. Decreases serum calcium by inhibiting mobilisation of bone calcium, decreasing intestinal absorption and increasing renal calcium and phosphate excretion. Acts via a G protein-coupled receptor on osteoclasts. Calcitonin derived from salmon is used in the treatment of severe hypercalcaemia, postmenopausal osteoporosis, Paget’s disease and intractable pain from bony metastases.

[Sir James Paget (1814–1899), English surgeon]

See also, Procalcitonin

Calcium. 99% of body calcium is contained in bone; plasma calcium consists of free ionised calcium (50%) and calcium bound to proteins (mainly albumin) and other ions. The free ionised form is a second messenger in many cellular processes, including neuromuscular transmission, muscle contraction, coagulation, cell division/movement and certain oxidative pathways. Binds to intracellular proteins (e.g. calmodulin), causing configurational changes and enzyme activation. Intracellular calcium levels are much higher than extracellular, due to relative membrane impermeability and active transport mechanisms. Calcium entry via specific channels leads to direct effects (e.g. neurotransmitter release in neurones), or further calcium release from intracellular organelles (e.g. in cardiac and skeletal muscle). Extracellular hypocalcaemia has a net excitatory effect on nerve and muscle; hypocalcaemic tetany can result in life-threatening laryngospasm.

Ionised calcium increases with acidosis, and decreases with alkalosis. Thus for accurate measurement, blood should be taken without a tourniquet (which causes local acidosis), and without hyper-/hypoventilation. Ionised calcium is measured in some centres, but total plasma calcium is easier to measure; normal value is 2.12–2.65 mmol/l. Varies with the plasma protein level; corrected by adding 0.02 mmol/l calcium for each g/l albumin below 40 g/l, or subtracting for each g/l above 40 g/l.

• Regulation:

ent vitamin D: group of related sterols. Cholecalciferol is formed in the skin by the action of ultraviolet light, and is converted in the liver to 25-hydroxycholecalciferol (in turn converted to 1,25-dihydroxycholecalciferol in the proximal renal tubules). Formation is increased by parathyroid hormone and decreased by hyperphosphataemia. Actions:

– increases intestinal calcium absorption.

– increases renal calcium reabsorption.

– increases bone mineralisation.

ent parathyroid hormone: secretion is increased by hypocalcaemia and hypomagnesaemia, and decreased by hypercalcaemia and hypermagnesaemia. Actions:

– mobilises bone calcium.

– increases renal calcium reabsorption.

– increases renal phosphate excretion.

– increases formation of 1,25-dihydroxycholecalciferol.

ent calcitonin: secreted by the parafollicular cells of the thyroid gland. Secretion is increased by hypercalcaemia, catecholamines and gastrin. Actions:

– decreases intestinal absorption of dietary calcium.

– inhibits mobilisation of bone calcium.

– increases renal calcium and phosphate excretion.

Calcium is used clinically to treat hypocalcaemia, e.g. during massive blood transfusion. It is also used as an inotropic drug. Although ionised calcium concentration may be low after cardiac arrest, its use during CPR is no longer recommended unless persistent hypocalcaemia, hyperkalaemia or overdose of calcium channel blocking drugs is involved. This is because of its adverse effects on ischaemic myocardium and on coronary and cerebral circulations.

Calcium chloride 10% contains 6.8 mmol/10 ml and 14.7% contains 10 mmol/10 ml; calcium gluconate 10% contains 2.2–2.3 mmol/10 ml, depending on the formulation. 5–10 ml calcium chloride or 10–20 ml calcium gluconate is usually recommended by slow iv bolus. The chloride preparation is usually recommended for CPR, although equal rises in plasma calcium are produced by gluconate, if equal amounts of calcium are given. Arrhythmias and prolonged hypercalcaemia may follow their use.

Aguilera IM, Vaughan RS (2000). Anaesthesia; 55: 779–90

Calcium channel blocking drugs. Structurally diverse group of drugs that block Ca²⁺ flux via specific Ca²⁺ channels (largely L-type, slow inward current). Effects vary according to relative affinity for cardiac or vascular smooth muscle Ca²⁺ channels.

• Classified according to pharmacological effects in vitro and in vivo:

ent class I: potent negative inotropic and chronotropic effects, e.g. verapamil. Acts mainly on the myocardium and conduction system; reduces myocardial contractility and O₂ consumption and slows conduction of the action potential at the SA/AV nodes. Thus mainly used to treat angina and SVT (less useful in hypertension). Severe myocardial depression may occur, especially in combination with β-adrenergic receptor antagonists.

ent class II: acts on vascular smooth muscle, reducing vascular tone; minimal direct myocardial activity (although may cause reflex tachycardia):

– nifedipine: acts mainly on coronary and peripheral arteries, with little myocardial depression. Used in angina, hypertension and Reynaud’s syndrome. Systemic vasodilatation may cause flushing and headache, especially for the first few days of treatment.

– nicardipine: as nifedipine, but with even less myocardial depression.

– amlodipine and felodipine: similar to nifedipine and nicardipine, but with longer duration of action and therefore taken once daily.

– nimodipine: particularly active on cerebral vascular smooth muscle, it is used to relieve cerebral vasospasm following subarachnoid haemorrhage.

ent class III: slight negative inotropic effects, without reflex tachycardia: diltiazem is used in angina and hypertension.

The above drugs act mainly on the L-type calcium (long-lasting) channels; these are more widely distributed than the T-type (transient) channels which are confined to the sinoatrial node, vascular smooth muscle and renal neuroendocrine cells. N-type calcium channels are concentrated in neural tissue and are the binding site of omega toxins produced by certain venomous spiders and cone snails. A derivative of the latter, ziconotide, is available for the treatment of chronic pain.

Additive effects might be expected between these drugs and the volatile anaesthetic agents, all of which decrease calcium entry into cells. Reduction in cardiac output, decreased atrioventricular conduction and vasodilatation may occur to different degrees, but severe interactions are rarely a problem in practice. Non-depolarising neuromuscular blockade may be potentiated.

Overdose causes hypotension, bradycardia and heart block. Treatment includes iv calcium chloride, glucagon and catecholamines. Heart block is usually resistant to atropine and hypotension may not respond to inotropes or vasopressors. High-dose insulin has been successful in reversing refractory hypotension.

Calcium resonium, see Polystyrene sulphonate resins

Calcium sensitisers. New class of inotropic drugs, now established as effective treatment of acute heart failure; examples include levosimendan and pimobendan. Act directly on cardiac myofilaments without increasing intracellular calcium, thus improving myocardial contractility without impairing ventricular relaxation. Levosimendan also has vasodilatory effects through opening of K⁺ channels.

Parissis JT, Rafouli-Stergiou P, Mebazaa A et al (2010). Curr Opin Crit Care; 16: 432–41

Calibration. Process of standardising the output of a measuring device against another measurement of known and constant magnitude. Reduces measurement error due to drift. One-point calibration is sufficient to address offset drift; two-point calibration is required for the mitigation of gradient drift. Essential for the accurate functioning of many measurement devices (e.g. arterial blood pressure monitor, blood gas analyser, expired gas analyser).

Calorie. Unit of energy. Although not an SI unit, widely used, especially when describing energy content of food.

1 cal = energy required to heat 1 g water by 1°C.

1 kcal (1 Cal) = energy required to heat 1 kg water by 1°C = 1000 cal.

1 cal = 4.18 joules.

Calorimetry, indirect, see Energy balance

CAM-ICU, see Confusion in the intensive care unit

cAMP, see Adenosine monophoshate, cyclic

Campbell–Howell method, see Carbon dioxide measurement

Canadian Journal of Anesthesia. Official journal of the Canadian Anesthetists’ Society. Launched in 1954 as the Canadian Anaesthetists’ Society Journal. Became the Canadian Journal of Anaesthesia in 1987 and the Canadian Journal of Anesthesia in 1999.

Candela. SI unit of luminous intensity, one of the base (fundamental) units. Definition relates to the luminous intensity of a radiating black body at the freezing point of platinum.

Cannabis. Hallucinogenic drug obtained from the Cannabis sativa plant. A mixture of at least 60 chemicals (cannabinoids) including the main psychoactive δ-9-tetra-hydrocannibinol. Cannabinoid receptors have been identified in central and peripheral neurones (CB₁ receptors) and lymphoid tissue (e.g. spleen) and macrophages (CB₂); both types are G protein-coupled receptors.

Therapeutic uses include treatment of glaucoma and as an antiemetic agent during chemotherapy. Also has analgesic, anticonvulsant and possibly antispasmodic properties, hence its use in chronic pain and multiple sclerosis. Mild psychological dependence is common, although physiological withdrawal states do not occur. Cognitive impairment, including psychosis with chronic usage, has been reported. Usually combined with tobacco and smoked; anaesthetic concerns are as for smoking generally.

Present law prohibits prescription of cannabis without a Home Office Licence and has hampered clinical trials; there has been pressure to allow freer administration in certain chronic conditions and even to decriminalise it altogether. Reclassified as a Class C drug under the Misuse of Drugs Act 1971 in 2004. Nabilone is a synthetic cannabinoid used as an antiemetic in chemotherapy-induced nausea and vomiting.

Hosking RD, Zajicek JP (2008). Br J Anaesth; 101: 59–68

Capacitance. Ability to retain electrical charge; defined as the charge stored by an object per voltage difference across it. The unit of capacitance is the farad (F), 1 farad being the capacity to store 1 coulomb of charge for an applied potential difference of 1 volt.

A capacitor composed of conductors separated by an insulator may be charged by a potential difference across it, but will not allow direct current to flow. Its stored charge may subsequently be discharged, e.g. in defibrillation. Repeated charging and discharging induced by an alternating current results in current flow across a capacitor.

[Michael Faraday (1791–1867), English chemist]

Capacitance vessels. Composed of venae cavae and large veins; normally only partially distended, they may expand to accommodate a large volume of blood before venous pressure is increased. Innervated by the sympathetic nervous system in the same way as the arterial system (resistance vessels), they act as a blood reservoir. 60–70% of blood volume is within the veins normally.

Capacitor, see Capacitance

Capillary circulation. Contains 5% of circulating blood volume, which passes from arterioles to venules via capillaries, usually within 2 s. Controlled by local autoregulatory mechanisms, and possibly by autonomic neural reflexes. Substances that readily cross the capillary walls (mainly by diffusion) include water, O₂, CO₂, glucose and urea. Hydrostatic pressure falls from about 30 mmHg (arteriolar end) to 15 mmHg (venous end) within the capillary. Direction of fluid flow across capillary walls is determined by hydrostatic and osmotic pressure gradients (Starling forces).

Capillary refill time. Time taken for capillaries to refill after blanching pressure is applied for 5 s. Normally < 2 s; prolonged in hypoperfusion and hypothermia. May be measured centrally, over the sternum, or peripherally, on the soft pad of a digit.

Capnography. Continuous measurement and pictorial display of CO₂ concentration (capnometry refers to measurement only). During anaesthesia, used to display end-tidal CO₂; this may be achieved using:

ent spectroscopy (most commonly infrared).

ent mass spectrometer.

The equipment used must have a very short response time in order to produce a continuous display (for uses and capnography traces, see Carbon dioxide, end-tidal).

Whitaker DK (2011). Anaesthesia; 66: 544–9

Capreomycin. Cyclic polypeptide antibacterial drug used to treat TB resistant to other therapy (especially in immunocompromised patients). Also used in other mycobacterial infections. Poorly absorbed orally, peak levels occur within 2 h of im injection. Excreted unchanged in the urine.

• Dosage: 1 g/day by deep im injection for 2–4 months, then 1 g 2–3 times weekly, reduced in renal failure.

• Side effects: renal and hepatic impairment, ocular disturbances, ototoxicity, blood dyscrasias, electrolyte disturbances, neuromuscular blockade.

Capsaicin. Component of hot chilli peppers; activates heat-sensitive Ca²⁺ channels (vanilloid receptors), located on Aδ and C pain fibres, producing a burning sensation. Initial stimulation is followed by depletion of substance P by reducing its synthesis, storage and transport. Applied topically for the treatment of neuralgias (e.g. postherpetic neuralgia) and arthritis. Should be applied 6–8-hourly. Takes 1–4 weeks to produce its effect. Application of a single high-concentration (8%) capsaicin patch can produce 3 months’ relief from neuropathic pain.

Captopril. Angiotensin converting enzyme inhibitor, used to treat hypertension and cardiac failure (including following MI), and diabetic nephropathy. Shorter acting than enalapril; onset is within 15 min, with peak effect at 30–60 min. Half-life is 2 h. Interferes with renal autoregulation; therefore contraindicated in renal artery stenosis or pre-existing renal impairment.

• Dosage: 6.25–50 mg orally bd/tds.

• Side effects: severe hypotension after the first dose, cough, taste disturbances, rash, abdominal pain, agranulocytosis, hyperkalaemia, renal impairment. Severe hypotension may occur after induction of anaesthesia and in hypovolaemia.

Contraindicated in pregnancy and porphyria.

Carbamazepine. Anticonvulsant drug, used to treat all types of epilepsy, except petit mal. Acts by stabilising the inactivated state of voltage-gated sodium channels. Has fewer side effects than phenytoin, and has a greater therapeutic index. Also used for pain management (e.g. in trigeminal neuralgia) and in manic-depressive disease.

• Dosage: initially 100–200 mg orally od/bd, increasing to up to 1.6 g/day in divided doses. Monitoring plasma levels may help determination of optimal dosage (target levels 20–50 µmol/l).

• Side effects: dizziness, visual disturbances, GIT upset, rash, hyponatraemia, cholestatic jaundice, hepatitis, syndrome of inappropriate ADH secretion. Blood dyscrasias may occur rarely. Enzyme induction may cause reduced effects of other drugs, e.g. warfarin.

Contraindicated in atrioventricular conduction defects and porphyria.

Carbapenems. Group of bactericidal antibacterial drugs; contain the β-lactam ring and thus, like the penicillins, impair bacterial cell wall synthesis. Include imipenem, meropenem and ertapenem.

Carbetocin. Analogue of human oxytocin, licensed for prevention of uterine atony after delivery by caesarean section under regional anaesthesia. Acts within 2 min of injection, its effects lasting over an hour.

• Dosage: 100 µg iv.

• Side effects: as for oxytocin.

Carbicarb. Experimental buffer composed of 0.3 M sodium carbonate and 0.3 M sodium bicarbonate; unlike bicarbonate, there is no net generation of CO₂, when treating acidosis.

Carbocisteine, see Mucolytic drugs

Carbohydrates (Saccharides). Class of compounds with the general formula C_a(H₂O)_b, hence their name, although they are not true hydrates. a usually exceeds 3, and may or not equal b. Notable examples of monosaccharides are ribose and glucose, where a = 5 and 6 respectively (pentoses and hexoses). Disaccharides are formed from condensation reactions between two monosaccharides (e.g. sucrose = glucose + fructose). Large polysaccharides include starch, cellulose and glycogen. Metabolites often contain phosphorus. Some polysaccharides are combined with proteins, e.g. mucopolysaccharides. Act as a source of energy in food, e.g.:

1 g carbohydrate yields about 17 kJ energy (4 Cal).

• Ingested carbohydrates are broken down thus:

ent mouth: salivary amylase: starch → smaller units

ent small intestine:

– pancreatic amylase: starch as above.

– maltase: maltose → glucose.

– lactase: lactose → glucose + galactose.

– sucrase: sucrose → glucose + fructose.

Hexoses and pentoses absorbed from the GIT pass to the liver for storage molecule synthesis or use in alternative metabolic pathways.

See also, Metabolism

Carbon dioxide (CO₂), Gas produced by oxidation of carbon-containing substances. Average rate of production under basal conditions in adults is about 200 ml/min, although it varies with the energy source (see Respiratory quotient).

• Partial pressures of CO₂:

ent inspired: 0.03 kPa (0.2 mmHg).

ent alveolar: 5.3 kPa (40 mmHg).

ent arterial: 5.3 kPa (40 mmHg).

ent venous: 6.1 kPa (46 mmHg).

ent expired: 4 kPa (30 mmHg).

Isolated in 1757 by Black. CO₂ narcosis was used for anaesthesia in animals by Hickman in 1824. Used to stimulate respiration during anaesthesia in the early 1900s, to maintain ventilation and speed uptake of volatile agents during induction; also used to assist blind nasal tracheal intubation. Administration is now generally considered hazardous because of the adverse effects of hypercapnia; CO₂ cylinders have now been largely removed from anaesthetic machines. Manufactured by heating calcium or magnesium carbonate, producing CO₂ and calcium/magnesium oxide.

• Properties:

ent colourless gas, 1.5 times denser than air.

ent mw 44.

ent boiling point −79°C.

ent critical temperature 31°C.

ent non-flammable and non-explosive.

ent supplied in grey cylinders; pressure is 50 bar at 15°C, about 57 bar at room temperature.

• Effects: as for hypercapnia.

[Joseph Black (1728–1799), Scottish chemist]

Carbon dioxide absorption, in anaesthetic breathing systems. Investigated and described by Waters in the early 1920s, although used earlier. Exhaled gases are passed over soda lime or a similar material (e.g. baralyme) and reused. In closed systems, only basal O₂ requirements need be supplied; absorption may also be used with low fresh gas flows and a leak through an expiratory valve.

• Advantages:

ent less wastage of inhalational agent.

ent less pollution.

ent warms and humidifies inhaled gases.

• Disadvantages:

ent if N₂O is also used, risk of hypoxic gas mixtures makes an O₂ analyser mandatory.

ent failure of CO₂ absorption may be due to exhaustion of soda lime or inefficient equipment; thus capnography is required.

ent resistance and dead space may be high with some systems, and inhalation of dust is possible.

ent trichloroethylene is incompatible with soda lime.

ent chemical reactions between the volatile agent and soda lime if the latter dries out excessively (see Soda lime).

• Methods:

ent circle systems.

ent Waters’ canister: cylindrical drum containing 0.45 kg soda lime. Reservoir bag at one end, facemask with fresh gas supply and expiratory valve at the other; exhaled gases pass to and fro through it. Most efficient when tidal volume equals the contained air space (400–450 ml). Smaller canisters are used for children. Dead space equals the volume between the patient and soda lime; it increases during use as the soda lime nearest the patient is exhausted. Efficiency is also reduced by channelling of exhaled gases through gaps in the soda lime if loosely packed and allowed to settle. Also heavy and bulky to use.

Carbon dioxide dissociation curve. Graph of blood CO₂ content against its PCO₂ (Fig. 29). The curve is much steeper than the oxyhaemoglobin dissociation curve, and more linear. Different curves are obtained for oxygenated and deoxygenated blood, the latter able to carry more CO₂ (Haldane effect). The difference between the dissolved CO₂ and the oxygenated haemoglobin curves represents the CO₂ carried as bicarbonate ion and carbamino compounds.

Fig. 29 Carbon dioxide dissociation curve

Carbon dioxide, end-tidal. Partial pressure of CO₂ measured in the final portion of exhaled gas. Approximates to alveolar PCO₂ in normal anaesthetised subjects; the difference is normally 0.4–0.7 kPa (3–5 mmHg), increasing with mismatch and increased CO₂ production. Continuous monitoring (e.g. using infrared capnography or mass spectrometry) is considered mandatory during general anaesthesia.

• Measurement is useful for assessing adequacy of ventilation, whether controlled or spontaneous, and allows normo- or hypocapnia to be produced as required during IPPV. Measurement also aids detection of:

ent efficient cardiac massage or return of spontaneous cardiac output in CPR.

ent oesophageal intubation, since CO₂ is only present in the oesophagus and stomach in small amounts, if at all.

ent PE (including fat and air embolism): P_ECO₂ falls due to increased alveolar dead space and reduced cardiac output.

ent rebreathing.

ent disconnection.

ent MH: P_ECO₂ rises as muscle metabolism increases.

• Display of a continuous trace is more useful than values alone (Fig. 30a):

ent phase 1: zero baseline during inspiration; a raised baseline indicates rebreathing (Fig. 30b).

ent phase 2: dead-space gas (containing no CO₂) is followed by alveolar gas, represented by a sudden rise to a plateau. Excessive sloping of the upstroke may indicate obstruction to expiration (Fig. 30c).

ent phase 3: near-horizontal plateau indicates mixing of alveolar gas. A steep upwards slope indicates obstruction to expiration or unequal mixing, e.g. COPD (Fig. 30c).

ent phase 4: rapid fall to zero at the onset of inspiration.

ent additional features may be present:

– superimposed regular oscillations corresponding to the heartbeat (Fig. 30d).

– small waves representing spontaneous breaths between ventilator breaths, e.g. if neuromuscular blockade is insufficient (Fig. 30e).

Fig. 30 End-tidal PCO₂ traces: (a) normal; (b) rebreathing; (c) expiratory obstruction; (d) superimposed heartbeats; (e) spontaneous breaths

Carbon dioxide measurement. Estimation of arterial PCO₂:

ent direct: Severinghaus CO₂ electrode consisting of a glass pH electrode separated from arterial blood sample by a thin membrane. CO₂ diffuses into bicarbonate solution surrounding the glass electrode, lowering pH. pH is measured and displayed in terms of PCO₂. Requires maintenance at 37°C, and calibration with known mixtures of CO₂/O₂ before use. Samples are stored on ice or analysed immediately, to reduce inaccuracy due to blood cell metabolism.

Indwelling intravascular CO₂ electrodes are available for continuous monitoring of PCO₂.

ent indirect:

– from gas:

– to obtain gas for analysis:

– end-tidal gas sampling (end-tidal PCO₂ approximates to alveolar PCO₂, which approximates to arterial PCO₂).

– rebreathing technique of Campbell and Howell: rebreathing from a 2 litre bag containing 50% O₂ for 90 s, then a further 30 s after 3 min rest. Bag PCO₂ then approximates to mixed venous PCO₂. Arterial PCO₂ is normally 0.8 kPa (6 mmHg) less than mixed venous PCO₂.

– subsequent gas analysis:

– chemical: formation of non-gaseous compounds, with reduction of overall volume of the gas mixture (Haldane apparatus).

– physical: capnography and mass spectrometry are most widely used. An interferometer or gas chromatography may also be used.

– from blood/tissues:

– transcutaneous electrode: requires heating of the skin; relatively inaccurate and slowly responsive.

– measurement of venous PCO₂ and capillary PCO₂: inaccurate and unreliable.

– Siggaard-Andersen nomogram: equilibration of the blood sample with gases of known PCO₂.

– van Slyke apparatus: liberation of gas from blood sample with subsequent chemical analysis.

– fibreoptic sensors: under development.

[John W Severinghaus, San Francisco anaesthetist; EJ Moran Campbell (1925–2004), English-born Canadian physiologist; John BL Howell, Southampton physician]

Carbon dioxide narcosis. Loss of consciousness caused by severe hypercapnia, i.e. arterial PCO₂ exceeding approximately 25 kPa (200 mmHg). Thought to be due to a profound fall in pH of CSF (under 6.9). Increasing central depression is seen at arterial PCO₂ greater than 13 kPa (100 mmHg), and CSF pH under 7.1. Other features of hypercapnia may be present.

Used by Hickman in 1824 to enable painless surgery on animals.

Carbon dioxide response curve. Graph defining the relationship between minute ventilation and arterial CO₂ tension. May be obtained by rebreathing from a 6 litre bag containing 50% O₂ and 7% CO₂, measuring minute ventilation and bag PCO₂ periodically. This is easier than increasing inspired CO₂ levels and measuring the response after equilibration at each new level. The curve may be used to indicate depression of respiratory drive (Fig. 31); increased threshold is represented by a shift of the curve to the right (1), and decreased sensitivity by depression of the slope (2). Both may follow administration of opioid and other depressant drugs, and in chronic hypercapnia; the opposite occurs in hypoxaemia.

See also, Breathing, control of

Fig. 31 Carbon dioxide response curve (see text)

Carbon dioxide transport. In arterial blood, approximately 50 ml CO₂ is carried per 100 ml blood, as:

ent bicarbonate: 45 ml.

ent carbonic acid: 2.5 ml.

ent carbamino compounds with proteins, mainly haemoglobin: 2.5 ml.

In venous blood, 54 ml is carried per 100 ml blood, as:

ent bicarbonate: 47.5 ml.

ent carbonic acid: 3.0 ml.

ent carbamino compounds: 3.5 ml.

CO₂ is rapidly converted by carbonic anhydrase in red cells to carbonic acid, which dissociates to bicarbonate and hydrogen ions. Bicarbonate passes into plasma in exchange for chloride ions (chloride shift); hydrogen ions are buffered mainly by haemoglobin. Haemoglobin’s buffering ability increases as it becomes deoxygenated, as does its ability to form carbamino groups (Haldane effect).

Carbon monoxide (CO). Colourless, odourless and tasteless gas produced by the partial oxidation of carbon-containing substances. Produced endogenously from the breakdown of haemoglobin, it acts as a neurotransmitter and may have a role in modulating inflammation and mitochondrial activity. Carbon monoxide poisoning may result from exposure to high levels of exogenous CO.

Carbon monoxide diffusing capacity, see Diffusing capacity

Carbon monoxide poisoning. May result from inhalation of fumes from car exhausts, fires, heating systems or coal gas supplies. Often coexists with cyanide poisoning. Although not directly toxic to the lungs, carbon monoxide (CO) binds to haemoglobin with 200–250 times the affinity of O₂, forming carboxyhaemoglobin, which dissociates very slowly. The amount of carboxyhaemoglobin formed depends on inspired CO concentration and duration of exposure.

Production of CO in circle systems has been reported under certain circumstances.

• Effects:

ent reduced capacity for O₂ transport.

ent oxyhaemoglobin dissociation curve shifted to the left.

ent inhibition of the cellular cytochrome oxidase system; tissue toxicity is proportional to the length of exposure.

ent aortic and carotid bodies do not detect hypoxia, since the arterial PO₂ is unaffected.

• Features:

ent non-specific if chronic, e.g. headache, weakness, dizziness, GIT disturbances.

ent if acute: as above, with hypoxia, convulsions and coma if severe.

ent the ‘cherry red’ colour of carboxyhaemoglobin may be apparent.

ent O₂ saturation measured by pulse oximetry may be misleading because carboxyhaemoglobin (which has a unique spectrophotometric profile) is interpreted as oxygenated haemoglobin by some devices. Newer co-oximeters (e.g. Masimo Rainbow) are specifically able to determine blood carboxyhaemoglobin levels by measuring the absorbance of light across a range of wavelengths, thus distinguishing between different species of haemoglobin.

ent neurological symptoms (e.g. dystonia, ataxia, parkinsonism), personality changes and impaired memory may follow recovery from CO coma.

• Treatment:

ent O₂ therapy: speeds carboxyhaemoglobin dissociation. Tracheal intubation and IPPV may be necessary. Elimination half-life of carbon monoxide is reduced from 4 h to under 1 h with 100% O₂; it is reduced further to under 30 min with hyperbaric O₂ at 2.5–3 atm. At this pressure, dissolved O₂ alone satisfies tissue O₂ requirements. Hyperbaric O₂ has been suggested if the patient is unconscious, has arrhythmias, is pregnant or has carboxyhaemoglobin levels above 40%.

ent carboxyhaemoglobin levels correlate poorly with severity of symptoms, because of variable effects of tissue toxicity. Values often quoted:

– 0.3–2%: normal non-smokers (some CO from pollution, some formed endogenously).

– 5–6%: normal smokers.

– 10–30%: mild symptoms common.

– above 60%: severe symptoms common.

Hampson NB, Piantadosi CA, Thom SR, Weaver LK (2012). Am J Respir Crit Care Med; 186: 1095–101

Carbon monoxide transfer factor, see Diffusing capacity

Carbonic anhydrase. Zinc-containing enzyme catalysing the reaction of CO₂ and water to form carbonic acid, which rapidly dissociates to bicarbonate and hydrogen ions. Absent from plasma, but present in high concentrations in:

ent red blood cells: important in buffering, CO₂ transport and O₂ transport.

ent renal tubular cells: important for maintaining acid–base balance.

ent gastric mucosa: important in hydrochloric acid production.

ent ciliary body: involved in aqueous humour formation. Inhibited by acetazolamide and sulphonamides.

Carboprost. Prostaglandin F_2α analogue, used for the induction of second-trimester abortion; also used to treat postpartum haemorrhage unresponsive to first-line therapy. Given as the trometamol salt.

• Dosage: 250 µg by deep im injection repeated as required every 15–90 min, up to 2 mg. May also be injected directly into the myometrium, although this carries increased risk of accidental iv administration and represents off-licence use.

• Side effects: vomiting, diarrhoea, leucocytosis, fever, bronchospasm, uterine rupture.

Carboxyhaemoglobin, see Carbon monoxide poisoning

Carcinogenicity of anaesthetic agents, see Environmental safety of anaesthetists; Fetus effects of anaesthetic agents on

Carcinoid syndrome. Results from secretion of vasoactive and other substances from certain tumours, found in the GIT (70%) or the bronchopulmonary system. Secreted compounds are metabolised by the liver so that symptoms are absent until hepatic metastases are present. May be associated with neurofibromatosis.

• Features:

ent flushing, mainly of the head and neck. May be associated with vasodilatation, hypotension, wheezing, skin wheals and sweating.

ent diarrhoea, sometimes with nausea and vomiting. Typically episodic, along with flushing. Weight loss is common.

ent endocardial fibrosis involving the tricuspid and pulmonary valves may cause right-sided cardiac failure.

Symptoms are traditionally ascribed to secretion of 5-HT (diarrhoea) and kinins (flushing), but many more substances have been implicated, e.g. dopamine, substance P, prostaglandins, histamine and vasoactive intestinal peptide. Diagnosis includes measurement of urinary 5-hydroxyindole acetic acid, a breakdown product of 5-HT.

• Anaesthetic management:

ent perioperative treatment with various drugs has been used to reduce hyper-/hypotensive episodes and bronchospasm:

– somatostatin analogues, e.g. octreotide: inhibits release of inflammatory mediators and has become the first-line treatment of many authorities.

– 5-HT antagonists: ketanserin, cyproheptadine, methysergide.

– antihistamine drugs.

ent invasive cardiovascular monitoring and careful fluid balance.

ent use of cardiostable drugs where possible; avoidance of drugs causing histamine release.

ent suxamethonium has been claimed to increase mediator release via fasciculations but this is uncertain.

ent drugs should be prepared for treatment of bronchospasm and hyper-/hypotension.

ent admission to HDU/ICU postoperatively.

Kinney MA, Warner ME, Nagorney DM, et al (2001). Br J Anaesth; 87: 447–52

Cardiac arrest. Sudden circulatory standstill. Common cause of death in cardiovascular disease, especially ischaemic heart disease. May also be caused by PE, electrolyte disturbances (e.g. of potassium or calcium), hypoxaemia, hypercapnia, hypotension, vagal reflexes, hypothermia, anaphylaxis, electrocution, drugs (e.g. adrenaline) and instrumentation of the heart.

• Features: unconsciousness within 15–30 s, apnoea or gasping respiration, pallor, cyanosis, absent pulses. Pupillary dilatation is usual.

• May be due to:

ent VF: usually associated with myocardial ischaemia. The most common ECG finding (about 60%), with the best prognosis.

ent asystole: occurs in about 30%. More likely in hypovolaemia and hypoxia, especially in children. May also follow vagally mediated bradycardia.

ent electromechanical dissociation (EMD)/pulseless electrical activity (PEA). May occur in widespread myocardial damage. The least common ECG finding, with the worst prognosis, unless due to mechanical causes of circulatory collapse, e.g. PE, cardiac tamponade, pneumothorax.

Asystole and EMD/PEA may convert to VF, which eventually converts to asystole if untreated.

Only 15–20% of patients leave hospital after cardiac arrest. Up to 30–40% survival is thought to be possible if prompt CPR is instituted. Permanent hypoxic brain damage usually occurs within 4–5 min unless CPR is instituted. The prognosis is better if the patient regains consciousness within 10 min of the circulation restarting.

Cardiac asthma. Acute pulmonary oedema resembling asthma. Both may feature dyspnoea, decreased lung compliance and widespread rhonchi, although pink frothy sputum is suggestive of pulmonary oedema. Increased airway resistance may result from true bronchospasm or from bronchial oedema.

Cardiac catheterisation. Passage of a catheter into the heart chambers for measurement of intracardiac pressures and O₂ saturations, or for injection of radiological contrast media for radiological imaging (angiocardiography). Used to investigate ischaemic heart disease, valvular heart disease and congenital heart disease; also used therapeutically (e.g. balloon valvotomy, atrial septostomy for transposition of the great arteries and percutaneous transluminal coronary angioplasty).

• Technique:

ent commonly performed under local anaesthesia except in small children, in whom general anaesthesia is required.

ent access is via a peripheral vein or artery, e.g. femoral or brachial vessels, using either a cut-down technique or percutaneous guidewire (Seldinger technique).

ent the right side of the heart is approached as for pulmonary artery catheterisation.

ent the left side of the heart is approached retrogradely under X-ray control, via a peripheral artery or from the right side through the atrial septum or a defect thereof.

• Information gained:

ent pressure values, waveforms and gradients between chambers.

ent saturation values; greater than expected values on the right side indicate a left-to-right shunt.

ent cardiac output may be measured using the Fick principle.

ent angiocardiography: cardiac function may be assessed on cine film, or the coronary vessels filled with dye to assess patency.

Approximate normal pressures and measurements are shown in Table 14.

Table 14 Normal pressures and O₂ saturations obtained during cardiac catheterisation

Site	Pressure (mmHg)	Saturation (%)
Right atrium	1–4	75
Right ventricle	25/4	75
Pulmonary artery	25/12	75
Left atrium	2–10	97
Left ventricle	120/10	97
Aorta	120/70	97

Fig. 32 Cardiac cycle (see text)

Cardiac compressions, see Cardiac massage

Cardiac contractility, see Myocardial contractility

Cardiac cycle. Sequence of events occurring during cardiac activity; often represented by the Wiggers’ diagram, which details changes in vascular pressures (especially arterial BP), heart chamber pressures, ECG and phonocardiography tracings during normal sinus rhythm (Fig. 32).

• Divided into five phases:

ent phase 1: atrial contraction: responsible for about 30% of ventricular filling. Some blood regurgitates into the venae cavae and pulmonary veins.

ent phase 2: isometric ventricular contraction: lasts from the closing of the tricuspid and mitral valves until ventricular pressures exceed aortic and pulmonary artery pressures, and the aortic and pulmonary valves open.

ent phase 3: ventricular ejection: most rapid at the start of systole. Lasts until the aortic and pulmonary valves close.

ent phase 4: isometric ventricular relaxation: lasts until the tricuspid and mitral valves open.

ent phase 5: passive ventricular filling: most rapid at the start of diastole.

• May also be described in terms of the changes in pressure and volume within the left ventricle during the cardiac cycle – the left ventricular pressure–volume ‘loop’ (Fig. 33):

ent consists of four phases corresponding to phases 2–5 of the Wigger’s diagram, as described above – the transition between phases is marked by opening/closure of mitral/aortic valves (MV/AV) (Fig. 33a).

ent stroke volume (SV) is the difference between end-diastolic volume (EDV) and end-systolic volume (ESV).

ent stroke work corresponds to the area within the loop.

ent changes in preload, afterload and myocardial contractility result in predictable changes in the shape of the loop, with corresponding changes in SV and work (Fig. 33b–d):

– increased preload or EDV results in increased force of contraction (see Starling’s law); SV and work increase.

– increased afterload results in increased ESV; SV decreases.

– increased contractility results in decreased ESV; stroke volume and work are increased.

Fig. 33 Left ventricular pressure–volume ‘loops’ (see text): (a) baseline; (b) increased preload; (c) increased afterload; (d) increased contractility (shaded loops show the effect of changes)

[Carl J Wiggers (1883–1963), US physiologist]

Cardiac enzymes. Enzymes normally within cardiac cells; released into the blood after injury (e.g. after MI or cardiac contusion), thus aiding diagnosis:

ent creatine kinase (CK or CPK):

– normally < 190 iu/l.

– rises 4–6 h after MI, peaks at 12 h, falls at 2–3 days.

– three specific isoenzymes exist for skeletal muscle (CKMM), brain (CKBB) and myocardium (CKMB). Presence of CKMB in the plasma indicates myocardial necrosis.

ent aspartate aminotransferase (AST):

– normally < 35 iu/l.

– rises after 12 h, peaks at 1–2 days.

ent lactate dehydrogenase (LDH):

– normally < 300 iu/l (depends on the assay).

– rises after 12 h, peaks at 2–3 days, falls after 5–7 days.

– five isoenzymes exist; an increase in the level of LDH1 or the ratio of LDH1:LDH2 indicates myocardial necrosis.

Have been largely replaced by troponins as indicators of myocardial damage (see Acute coronary syndromes).

Cardiac failure. Usually defined as inability of the heart to produce sufficient output for the body’s requirements. The diagnosis is clinical, ranging from mild symptoms on exertion only to cardiogenic shock. Several terms have been used to describe different forms of cardiac failure:

ent left or right ventricular failure (the most commonly used classification). The left ventricle is usually affected by general disease because its workload is much greater than that of the right.

ent forward or backward failure: the former refers to failure with reduced cardiac output; the latter refers to failure with venous congestion.

ent congestive cardiac failure: the term sometimes refers to backward failure, but is often reserved for left-sided failure leading to right-sided failure.

ent high-output failure: associated with increased preload and increased cardiac output.

ent diastolic failure: recently recognised form in which the ejection fraction may be normal but ventricular filling is impaired.

• Caused by:

ent increased workload:

– preload:

– aortic/mitral regurgitation.

– ASD/VSD.

– severe anaemia, fluid overload, hyperthyroidism.

– afterload:

– hypertension.

– pulmonary/aortic stenosis, hypertrophic obstructive cardiomyopathy.

– pulmonary hypertension, PE.

ent reduced force of contraction:

– MI, ischaemic heart disease.

– cardiomyopathy.

– arrhythmias.

– myocarditis.

ent reduced filling:

– tricuspid/mitral stenosis.

– cardiac tamponade, constrictive pericarditis (right side).

– reduced ventricular compliance, e.g. amyloid infiltration.

• Effects:

ent ventricular end-diastolic pressure increases, leading to compensatory mechanisms:

– ventricular hypertrophy.

– increased force of contraction (Starling’s law).

– neuroendocrine response: mainly increased sympathetic activity, with tachycardia, vasoconstriction and increased contractility. Aldosterone, renin/angiotensin and vasopressin activity are increased, especially in chronic failure, but mechanisms are unclear. Salt and water retention result.

ent ventricular compliance is reduced, leading to increased atrial pressure and atrial hypertrophy. Eventually, ventricular dilatation occurs, with higher wall tension required to produce a given pressure (Laplace’s law).

ent coronary blood flow is reduced by tachycardia, raised end-diastolic pressure and increased muscle mass.

ent left-sided failure may lead to pulmonary oedema, pulmonary hypertension, mismatch, decreased lung compliance and right-sided failure.

ent right ventricular failure: CVP and JVP increase, with peripheral oedema and hepatic engorgement.

ent reduced peripheral blood flow leads to increased O₂ uptake and reduction of mixed venous PO₂.

ent sodium and water retention exacerbate oedema.

• Features:

ent reduced cardiac output may result in hypotension, confusion and coma.

ent left-sided failure:

– dyspnoea, typically worse on lying flat (orthopnoea) and sometimes waking the patient at night (paroxysmal nocturnal dyspnoea).

– peripheral shutdown, basal crepitations, left ventricular hypertrophy. Extra heart sounds, e.g. gallop rhythm and heart murmurs, may be present. Cheyne–Stokes respiration may accompany low output.

– acute pulmonary oedema.

ent right-sided failure:

– raised JVP.

– dependent oedema, e.g. ankles if ambulant, sacrum if bed-bound.

– hepatomegaly/ascites; the liver may be tender.

– right ventricular hypertrophy.

ent CXR may reveal cardiomegaly, upper-lobe blood diversion, fluid in the pulmonary fissures, Kerley lines, pleural effusion and pulmonary oedema. ECG may reveal ventricular hypertrophy and strain and arrhythmias.

• Management:

ent general: of underlying cause, rest, sodium restriction; O₂ therapy if acute.

ent ACE inhibitors: inhibit ventricular remodelling, reducing mortality and morbidity. Angiotensin II receptor antagonists have similar efficacy.

ent diuretics: reduce salt and water retention, providing symptomatic relief; a thiazide in combination with a loop diuretic is frequently used. Spironolactone may be added in low dosage to ACE inhibitor/diuretic therapy in severe, non-responsive failure.

ent β-adrenergic receptor antagonists (e.g. carvedilol, bisoprolol): first-line agents in stable left ventricular systolic failure, reducing mortality and morbidity.

ent other vasodilator drugs (e.g. nitrates, hydralazine) have been used in patients unable to tolerate ACE inhibitors.

ent inotropic drugs: oral drugs are mostly disappointing. The most effective drugs are administered by iv infusion.

ent digoxin: may improve symptoms and performance but not mortality.

ent calcium sensitisers, e.g. levosimendan.

ent atrial-synchronised biventricular pacemakers have been shown to improve symptoms and mortality in patients with severe failure.

ent emergency treatment: as for pulmonary oedema and cardiogenic shock.

• Response to treatment (Fig. 34):

ent 1: inotropic drugs/arterial vasodilators.

ent 2: diuretics/venous vasodilators.

ent 3:

– drug combinations, e.g. inotropes + vasodilators; often produce the greatest improvement

– intra-aortic counter-pulsation balloon pump.

Fig. 34 Response to treatment of cardiac failure by Starling’s curve (see text)

• Anaesthetic considerations:

ent cardiac failure is consistently associated with increased perioperative morbidity and mortality; it should therefore be treated preoperatively whenever possible.

ent treatment as above. Electrolyte disturbances and digoxin toxicity may occur.

ent anaesthetic drugs should be given in small doses and slowly, because:

– arm–brain circulation time is increased.

– increased proportion of cardiac output goes to vital organs, e.g. brain and heart; thus greater effects are seen on these organs than in normal cardiac output states.

ent danger of myocardial depression, hypoxia, arrhythmias.

ent use of epidural/spinal anaesthesia is controversial; the benefit of reduction of SVR may be offset by the risk of hypotension. Perioperative risk is not diminished.

McMurray JJV (2010). N Engl J Med; 362: 228–38

Cardiac glycosides. Drugs derived from plant extracts; used to control ventricular rate in atrial fibrillation and atrial flutter and for symptomatic relief in cardiac failure. Actions are due to inhibition of the sodium/potassium pump and increased calcium mobilisation. The drugs have long half-lives (e.g. ouabain 20 h; digoxin 36 h; digitoxin 4 days), large volumes of distribution (e.g. digoxin 700 litres) and low therapeutic index.

• Actions:

ent increase myocardial contractility and stroke volume.

ent decrease heart rate via direct effects on atrioventricular conduction and sinus node discharge; also act indirectly by increasing vagal tone.

• Side effects: as for digoxin. They are increased by hypokalaemia, hypercalcaemia and hypomagnesaemia. Toxicity is also more likely in renal failure and pulmonary disease.

Digoxin is most widely used. Ouabain is more rapidly acting.

Cardiac index (CI). Cardiac output corrected for body size, expressed in terms of body surface area:

Normal value is 2.5–4.2 l/min/m².

Cardiac massage. Periodic compression of the heart or chest in order to maintain cardiac output, e.g. during CPR. Both open (internal) and closed (external) cardiac massage were developed in the late 1800s. The latter became more popular in the 1960s following clear demonstration of its value in dogs and humans, and was subsequently adopted by the American Heart Association and the Resuscitation Council (UK) as method of choice.

• Closed cardiac massage:

ent with the patient supine on a rigid surface, the heel of one hand is placed on the lower half of the sternum. The other hand is placed on the first, with fingers clear of the chest. With elbows straight and shoulders vertically above the hands, regular compressions are applied, with a compression : relaxation ratio of 1 : 1. The sternum should be depressed 5–6 cm at each compression, at a rate of 100–120/min.

ent efficacy is assessed by feeling the femoral or carotid pulse, although palpable peak pressures may not reflect blood flow. End-tidal CO₂ measurement has been used to assess adequacy of massage; an increase reflects improved cardiac output.

ent may produce up to 30% of normal cardiac output with corresponding carotid and cerebral blood flow. Coronary flow is low during cardiac massage, and falls rapidly when massage is stopped.

ent Technique in children up to 8 years:

– under 1 year: tips of two fingers placed on the sternum, one finger’s breadth below a line joining the nipples. The sternum is depressed by one-third of the depth of the child’s chest at a rate of 100–120/min.

– up to 8 years: heel of one hand placed over the lower half of the sternum, the fingers lifted to avoid applying pressure on the ribs. The sternum is depressed by one-third of the depth of the child’s chest at a rate of 100–120/min.

ent theories of mechanism (both may occur):

– cardiac pump (as originally suggested): the heart is squeezed between sternum and vertebrae during compressions, expelling blood from the ventricles. During relaxation, blood is drawn into the chest by negative intrathoracic pressure, and the ventricles fill from the atria (‘thoracic diastole’). Thought to be more important in children and when the heart is large.

– thoracic pump: the theory arose from arterial and cardiac chamber pressure measurements during CPR, and from the phenomenon of cough–CPR. Positive intrathoracic pressure pushes blood out of heart and chest during compressions; reverse flow is prevented by cardiac and venous valves, and collapse of the thin-walled veins. During relaxation, blood is drawn into the chest by negative intrathoracic pressure.

Intrathoracic pressures may be maximised by synchronising compressions with IPPV breaths, with or without abdominal binding or compression (‘new’ CPR). Devices used to augment the thoracic pump mechanism include:

– automatic chest compressor (‘chest thumper’).

– ‘active compression/decompression’ device: applies suction to the chest wall between compressions to increase venous return.

– impedance valve inserted in the ventilating system: impedes passive inspiration during the ‘release’ phase, thus increasing intrathoracic negative pressure and increasing venous return. During compression the extra venous return results in greater cardiac output.

Improved blood flows and outcome have been claimed but further studies are awaited.

• Open cardiac massage:

ent increasingly used, because blood flows and cardiac output are greater than with closed massage. Also, direct vision and palpation are useful in assessing cardiac rhythm and filling, and defibrillation and intracardiac injection are easier.